Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal transplantation is frequently accompanied by systemic hypertension. In the present study we evaluated the effect of 2.5 mg lisinopril in 12 hypertensive and proteinuric renal graft recipients with stable graft function over 3 months. Only patients with absence of renal artery stenosis, at least as judged by technetium-scan imaging, were included. Lisinopril was effective in lowering systemic blood pressure. Mean arterial pressure was unchanged despite reduction of concomitant antihypertensive medication. Mean serum creatinine was unchanged during the study (1.95 +/- 0.8 mg/dl in the pretreatment period vs. 1.77 +/- 0.76 mg/dl in the intervention period, n.s.). Glomerular filtration rate remained stable (62.75 +/- 21.96 vs. 60.17 +/- 18.27 ml/min/1.73 m2, n.s.) whereas renal plasma flow increased (224.75 +/- 91.66 vs. 244.92 +/- 94.13 ml/min/1.73m2, P < 0.01), leading to a drop in filtration fraction (31.4 +/- 12.4 vs. 26.8 +/- 8.6, n.s.). Renal vascular resistance was significantly reduced following angiotensin-converting enzyme (ACE) inhibitor therapy (26,447 +/- 14,574 vs. 23,425 +/- 12,430 dyne sec cm-5/1.73 m2, P < 0.01). Mean daily proteinuric decreased significantly (2.98 +/- 2.06 vs. 2.06 +/- 2.29 g, P < 0.01) whereas in a group of patients with comparable blood pressure but without ACE inhibitor therapy and similar degree of proteinuria, 24-hr proteinuria remained stable. No severe side effects were observed--in particular, mean serum potassium showed only a slight increase and no clinically significant hyperkalemic condition was observed. When lisinopril therapy was withdrawn after 3 months, blood pressure increased in all patients, requiring reinstitution of additional antihypertensive medication. Renal hemodynamic parameters and daily proteinuria returned to baseline values. We conclude that 2.5 mg lisinopril daily was safe and effective in this group of renal transplant recipients and showed a good antihypertensive as well as antiproteinuric effect.
 ...
PMID:The effects of lisinopril on renal function in proteinuric renal transplant recipients. 839 Jul 33

We studied 25 patients with hypertension documented through ambulatory blood pressure monitoring (ABPM) to know the antihypertensive effect of Lisinopril and its action throughout the day. ABPM was done in all patients after two weeks of washout (phase 1). Then patients took 20 mg daily of Lisinopril during four weeks and after that ABPM was repeated (phase 2). Finally, those patients who persisted with high blood pressure received 40 mg daily of Lisinopril during four more weeks and again ABPM was repeated (phase 3). We found statistic difference in the systolic and diastolic blood pressure among the three phases. During the first phase there were 17 patients (68%) with high blood pressure and this number decreased to 8 (32%) in the second one and to 7 (28%) in the third phase. The results show that Lisinopril has satisfactory antihypertensive effect in about 40% of patients. Nevertheless 20% of the case remained with high blood pressure despite treatment with 40 mg of Lisinopril. On the other hand, both, systolic and diastolic blood pressure decreased satisfactory during the night with the dosage received in the morning. We concluded that Lisinopril has moderate effect when it is given as monotherapy and, it has satisfactory effect all over the day.
 ...
PMID:[The antihypertensive effect of lisinopril in a single daily dosage. A study of arterial pressure with ambulatory monitoring]. 867

In this study we evaluated in hypertensive patients the effects of drug-induced left ventricular hypertrophy regression on cardiac autonomic control, as assessed by means of heart period variability analysis. Power spectral analysis of 24-hour electrocardiographic monitoring was performed in 30 hypertensive patients with left ventricular hypertrophy at baseline, after 1 year of lisinopril treatment, and after 1 month of drug withdrawal. At the same times, patients underwent 24-hour blood pressure monitoring, echocardiographic study, and plasma renin activity assessment. Lisinopril treatment increased plasma renin activity and reduced 24-hour systolic and diastolic pressures (from 159 +/- 14 to 121 +/- 8 and from 103 +/- 7 to 80 +/- 3 mm Hg, respectively) and left ventricular mass index (from 159 +/- 33 to 134 +/- 26 g/m2); moreover, in 12 of 30 patients, left ventricular mass normalization was achieved. Drug withdrawal was followed by an increase in blood pressure without left ventricular mass modification. In the total study population, only high-frequency power was higher after lisinopril treatment. In the subgroup of patients with left ventricular mass normalization, daytime and nighttime high-frequency powers as well as nighttime total and very-low-frequency powers were higher after 1 year of treatment than at baseline. In the remaining 18 patients, power spectral measures after treatment were slightly lower than at baseline and were even lower after drug withdrawal. Thus, in hypertensive hypertrophic patients, lisinopril treatment improves sympathovagal imbalance when left ventricular mass normalization is achieved. In patients without left ventricular mass normalization, drug withdrawal is followed by a worsening of neural cardiac control.
Hypertension 1996 Mar
PMID:Effect of 1 year of lisinopril treatment on cardiac autonomic control in hypertensive patients with left ventricular hypertrophy. 869 34

Following establishment of its efficacy in hypertension and congestive heart failure, the ACE inhibitor lisinopril has now been shown to reduce mortality and cardiovascular morbidity in patients with myocardial infarction when administered as early treatment. The ability of lisinopril to attenuate the detrimental effects of left ventricular remodelling is a key mechanism; however, additional cardioprotective and vasculoprotective actions are postulated to play a role in mediating the early benefit. The GISSI-3 trial in > 19 000 patients has demonstrated that, when given orally within 24 hours of symptom onset and continued for 6 weeks, lisinopril (with or without nitrates) produces measurable survival benefits within 1 to 2 days of starting treatment. Compared with no lisinopril treatment, reductions of 11% in risk of mortality and 7.7% in a combined end-point (death plus severe left ventricular dysfunction) were evident at 6 weeks. Advantages were apparent in all types of patients. Thus, those at high risk-women, the elderly, patients with diabetes mellitus and those with anterior infarct and/or Killip class > 1 -also benefited. These gains in combined end-point events persisted in the longer term, despite treatment withdrawal after 6 weeks in most patients. At 6 months, the incidence rate for the combined end-point remained lower than with control (a 6.2% reduction). The GISSI-3 results concur with those from recent large investigations (ISIS-4, CCS-1, SMILE) of other ACE inhibitors as early management in myocardial infarction. However, the results of the CONSENSUS II trial (using intravenous enalaprilat then oral enalapril) were unfavourable in some patients. These findings, together with the development of persistent hypotension and, to a lesser extent, renal dysfunction among patients in the GISSI-3 trial, have prompted considerable debate over optimum treatment strategies. Present opinion generally holds that therapy with lisinopril or other ACE inhibitors shown to be beneficial may be started within 24 hours in haemodynamically stable patients with no other contraindications; current labelling in the US and other countries reflects this position. There is virtually unanimous agreement that such therapy is indicated in high-risk patients, particularly those with left ventricular dysfunction. The choice of ACE inhibitor appears less important than the decision to treat; it seems likely that these benefits are a class effect. Lisinopril has a tolerability profile resembling that of other ACE inhibitors, can be given once daily and may be less costly than other members of its class. However, present cost analyses are flawed and this latter points remains to be proven in formal cost-effectiveness analyses. In conclusion, early treatment with lisinopril (within 24 hours of symptom onset) for 6 weeks improves survival and reduces cardiovascular morbidity in patients with myocardial infarction, and confers ongoing benefit after drug withdrawal. While patients with symptoms of left ventricular dysfunction are prime candidates for treatment, all those who are haemodynamically stable with no other contraindications are also eligible to receive therapy. Lisinopril and other ACE inhibitors shown to be beneficial should therefore be considered an integral part of the early management of myocardial infarction in suitable patients.
 ...
PMID:Lisinopril. A review of its pharmacology and clinical efficacy in the early management of acute myocardial infarction. 889 68

Recent studies have shown that angiotensin-(1-7) [Ang-(1-7)] interacts with kinins and augments bradykinin (BK)-induced vasodilator responses by an unknown mechanism. In this study, we evaluated whether the potentiation of the BK-induced vasodilation by Ang-(1-7) may be attributable to inhibition of BK metabolism, release of nitric oxide, or both. Isometric tension was measured in intact canine coronary artery rings suspended in organ chambers. 125I-[Tyr0]-BK metabolism was determined in vascular rings by assessing the degradation of the peptide by high-performance liquid chromatography. Ang-(1-7) augmented the vasodilation induced by BK in a concentration-dependent manner in rings preconstricted with the thromboxane analog U46619. The EC50 of BK (2.45 +/- 0.51 nmol/L versus 0.37 +/- 0.08 nmol/L) was shifted leftward by 6.6-fold in the presence of 2 mumol/L concentration of Ang-(1-7). The response was specific for BK. since Ang-(1-7) did not augment the vasodilation induced by either acetylcholine (0.05 mumol/L) or sodium nitroprusside (0.1 mumol/L). Moreover, neither angiotensin I nor angiotensin II (Ang II) duplicated the augmented BK response of Ang-(1-7). Pretreatment of vascular rings with the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NA; 100 mumol/L) completely abolished the effects of Ang-(1-7) on BK-induced vasodilation whereas pretreatment with indomethacin (10 mumol/L) was without effect. The potent specific BK B2 receptor antagonist, Hoe 140. nearly abolished the BK and the Ang-(1-7) potentiated responses at 2 mumol/L, whereas at a lower concentration (20 nmol/L) Hoe 140 shifted the response curve to the right for both Ang-(1-7) and vehicle; however, the augmented response to Ang-(1-7) persisted. Preincubation of vascular rings with 20 mumol/L of the AT1 (CV11974), AT2 (PD123319), or nonselective (Sar1 Thr8-Ang II) receptor antagonists had no significant effect on the Ang-(1-7)-enhanced vasodilator response to BK. Lisinopril (2 mumol/L) significantly enhanced the BK-induced vasodilator response while at the same time it abolished the synergistic action of Ang-(1-7) on BK. In addition, pretreatment with 2 mumol/L Ang-(1-7) significantly inhibited the degradation of 125I-[Tyr0]-BK and the appearance of the BK-(1-7) and BK-(1-5) metabolites in coronary vascular rings. Ang-(1-7) inhibited purified canine angiotensin converting enzyme activity with an IC50 of 0.65 mumol/L. In conclusion. Ang-(1-7) acts as a local synergistic modulator of kinin-induced vasodilation by inhibiting angiotensin converting enzyme and releasing nitric oxide.
Hypertension 1997 Jan
PMID:Angiotensin-(1-7) augments bradykinin-induced vasodilation by competing with ACE and releasing nitric oxide. 903 33

Lisinopril, the lysine analogue of enalaprilat, is a long-acting angiotensin converting enzyme (ACE) inhibitor which is administered once daily by mouth. The efficacy of lisinopril in reducing blood pressure is well established in younger populations, and many trials now show it to be effective in lowering blood pressure in elderly patients with hypertension. In comparative and non-comparative clinical trials, 68.2 to 89.1% of elderly patients responded (diastolic pressure < or = 90 mm Hg) to > or = 8 weeks' lisinopril treatment. Age-related differences in antihypertensive efficacy do not appear to be clinically significant, and dosages effective in elderly patients tend to range from 2.5 to 40 mg/day. Dosages usually need to be lower in patients with significant renal impairment. In congestive heart failure, lisinopril 2.5 to 20 mg/day increases exercise duration, improves left ventricular ejection fraction and has no significant effect on ventricular ectopic beats. It is similar in efficacy to enalapril and digoxin and similar or superior to captopril on most end-points. Data from the GISSI-3 post-myocardial infarction trial show that lisinopril reduced mortality and left ventricular dysfunction when given for 42 days starting within 24 hours of the onset of infarction symptoms. Results at 6 weeks and 6 months were similar in elderly and younger patients. Elderly patients, however, among other subgroups, exhibited a strong reduction in risk of low ejection fraction after treatment (-25.5%). Economic studies suggest that lisinopril is cost saving compared with other ACE inhibitors in some markets. When given according to the GISSI-3 protocol, lisinopril appears to be one of the less expensive of the successful ACE inhibitor regimens for acute myocardial infarction. In other trials, patients with diabetic nephropathy and hypertension improved or did not deteriorate during lisinopril treatment. Blood pressure was controlled and reductions or trends towards reductions in albuminuria were observed. These reductions were similar to those in diltiazem, nifedipine and verapamil recipients, and greater than those in patients receiving atenolol. Lisinopril appears to reduce mortality in diabetic patients after myocardial infarction and may also improve neuropathy associated with diabetes. Lisinopril is well tolerated and the profile of adverse events seen is typical of ACE inhibitors as a class. There is a tendency for more elderly than younger patients to discontinue treatment, but this trend is not clearly related to the incidence of adverse events in these age groups. Drug interactions occur with few other agents and are usually clinically significant only between lisinopril and either diuretics or lithium. Lisinopril is, thus, an effective treatment for elderly patients with hypertension, congestive heart failure and acute myocardial infarction and has shown promising benefits in patients with diabetic nephropathy.
 ...
PMID:Lisinopril. A review of its pharmacology and clinical efficacy in elderly patients. 906 Dec 70

Arterial hypertension may be associated with altered left ventricular filling dynamics. The specific goal of this study was to evaluate whether short-term administration of the ACE inhibitor lisinopril in hypertensive patients with an altered diastolic pattern induced an improvement of left ventricular dynamics, assessed by the echocardio-Doppler technique, independently of effects on left ventricular mass. In a double-blind cross-over study 39 essential hypertensive patients with a ratio of peak early to peak atrial velocity (E/A) < 1 were randomized, after a run-in period of 2 weeks without any antihypertensive treatment, to receive lisinopril (20 mg once a day) and placebo for 4 weeks, respectively. At the end of both the run-in and the treatment periods, blood pressure and heart rate were measured and an echocardio-Doppler examination was carried out. The echocardio-Doppler evaluation was performed both at rest and at the peak of a hand-grip test (3 min at 30% of maximal strength). Left ventricular dimensions were obtained from two-dimensionally guided M-mode tracings using the criteria of the American Society of Echocardiography. Left ventricular peak filling rates and filling rate integrals were measured by a pulsed Doppler technique. Lisinopril caused a significant reduction in systolic and diastolic blood pressure at rest (-13/-9 mmHg vs baseline values, p < 0.05; -6/-4 mmHg vs placebo values, p < 0.05) and during isometric exercise (-17/-9 mmHg vs baseline period, p < 0.05; -6/-5 mmHg vs placebo, p < 0.05). Lisinopril did not induce any significant change in left ventricular structure and systolic function. All the left ventricular filling parameters considered (E velocity, A velocity, E/A ratio) both at rest and during isometric exercise did not significantly differ after lisinopril treatment when compared to those obtained in basal conditions and after placebo administration. This double-blind cross-over study demonstrates that short-term afterload reduction induced by lisinopril does not modify altered diastolic dynamics in hypertensive patients. Diastolic dysfunction of the left ventricle is a complex process influenced by a number of functional and structural factors and apparently cannot be significantly improved by short-term blood pressure reduction by antihypertensive therapy.
 ...
PMID:Lack of effect of short-term lisinopril administration on left ventricular filling dynamics in hypertensive patients with diastolic dysfunction. 936 2

Left ventricular hypertrophy (LVH), which frequently occurs in chronic uremia, may be due in part to factors other than arterial hypertension, chronic anemia, and/or other well-known loading conditions inherent to the uremic state. Angiotensin-converting enzyme (ACE) inhibitors may be able to reverse LVH by mechanisms independent of their antihypertensive effects. In this study, 18 subjects free of arterial hypertension or severe anemia were selected from 170 chronically hemodialyzed uremic patients after fulfilling the criterion of a supranormal left ventricular mass (LVM). Ten subjects agreed to undergo treatment with 2.5 to 20 mg lisinopril every other day over a period of 2 years, during which annual determinations of the LVM by echocardiography and of the 24-hour blood pressure with a portable device were carried out. Eight patients unwilling to undergo the treatment served as controls. The average resting left ventricular mass index (LVMi) of the overall group was 178 +/- 30 g/m2 body surface area (+/- SD), and did not differ between the two subgroups. Lisinopril treatment significantly decreased the LVM of eight of 10 treated subjects and actually even completely normalized it in three. The LVM of the untreated group remained unchanged. Systolic and diastolic blood pressures were 138 +/- 5 mm Hg and 78 +/- 6 mm Hg in the treated group and 133 +/- 9 mm Hg and 75 +/- 4 mm Hg in the untreated group, respectively (P = NS), and did not vary over the following 2 years. This study indicates that a mild degree of LVH, which is seemingly independent of arterial blood pressure load, does exist in a tight subset of uremic patients. This study also demonstrates that this type of LVH is apparently nonprogressive. ACE inhibitors given at doses not affecting blood pressure are able to reverse it.
 ...
PMID:Prolonged therapy with ACE inhibitors induces a regression of left ventricular hypertrophy of dialyzed uremic patients independently from hypotensive effects. 937 Jan 81

The objectives of our study were to assess the reproducibility of the trough-to-peak ratio (T/P) and to see whether a high T/P is accompanied by more organ protection or vice versa. The study included 175 (mean+/-SD age, 51+/-9 years) subjects with mild-moderate essential hypertension who had echocardiographic evidence of left ventricular (LV) hypertrophy taken from the SAMPLE study (Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation), an open-label multicenter study. The study included a 3-week washout pretreatment period, a 12-month treatment period with lisinopril (n=84) or lisinopril plus hydrochlorothiazide (n=91) once daily, and a 4-week placebo follow-up period. Results of 24-hour ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index (LVMI) were obtained before and after 3 and 12 months of treatment. T/Ps were computed in each patient by dividing the systolic and diastolic blood pressure changes at trough (changes in the last 2 hours of the monitoring period) by those at peak (average of the 2 adjacent hours with the maximal blood pressure reduction between the 2nd and 8th hour from drug intake) after 3 and 12 months of treatment. Average 24-hour blood pressure was similarly reduced at 3 and 12 months. Trough blood pressure changes at 3 and 12 months were closely correlated, as were the corresponding peak blood pressure changes. However, the 3- and 12-month T/Ps correlated to a lesser degree (r<0.42). Furthermore, the reduction of LVMI induced by treatment was similarly correlated with the treatment-induced reduction in 24-hour average, trough, and peak blood pressures but not with the T/Ps. This was also evident when the contribution to LV hypertrophy regression by 24-hour blood pressure changes and T/Ps was assessed in a multivariate regression analysis. In patients with a T/P >/=0.5 or <0.5, the regression of LVMI was similar. In conclusion, peak and trough blood pressure changes are reproducible and predict the regression of LVMI induced by treatment as well as average 24-hour blood pressure. T/Ps are less reproducible, and their value does not predict regression of organ damage by antihypertensive treatment.
Hypertension 1998 Sep
PMID:Reproducibility and clinical value of the trough-to-peak ratio of the antihypertensive effect: evidence from the sample study. 974 Jun 6

We determined the mechanism accounting for the removal and metabolism of angiotensin-(1-7) [Ang-(1-7)] in 21 anesthetized spontaneously hypertensive (SHR), 18 age-matched normotensive Sprague-Dawley (SD), and 36 mRen-2 transgenic (TG+) rats. Animals of all 3 strains were provided with tap water or tap water containing losartan, lisinopril, or a combination of lisinopril and losartan for 2 weeks. On the day of the experiment, Ang-(1-7) was infused for a period of 15 minutes at a rate of 278 nmol . kg-1 . min-1. After this time, samples of arterial blood were collected rapidly at regular intervals for the assay of plasma Ang-(1-7) levels by radioimmunoassay. Infusion of Ang-(1-7) had a minimal effect on vehicle-treated SD rats but elicited a biphasic pressor/depressor response in vehicle-treated SHR and TG+ rats. In lisinopril-treated rats, Ang-(1-7) infusion increased blood pressure, whereas losartan treatment abolished the pressor component of the response without altering the secondary fall in arterial pressure. Combined treatment with lisinopril and losartan abolished the cardiovascular response to Ang-(1-7) in all 3 strains. In vehicle-treated SD, SHR and TG+ the half-life (t1/2) of Ang-(1-7) averaged 10+/-1, 10+/-1, and 9+/-1 seconds, respectively. Lisinopril alone or in combination with losartan produced a statistically significant rise in the half-life of Ang-(1-7) in all 3 strains of rats. Plasma clearance of Ang-(1-7) was significantly greater in the untreated SD rats compared with either the SHR or TG+ rat. Lisinopril treatment was associated with reduced clearance of Ang-(1-7) in all 3 strains. Concurrent experiments in pulmonary membranes from SD and SHR showed a statistically significant inhibition of 125I-Ang-(1-7) metabolism in the presence of lisinopril. These studies showed for the first time that the very short half-life of Ang-(1-7) in the circulation is primarily accounted for peptide metabolism by ACE. These findings suggest a novel role of ACE in the regulation of the production and metabolism of the two primary active hormones of the renin angiotensin system.
Hypertension 1998 Sep
PMID:Converting enzyme determines plasma clearance of angiotensin-(1-7). 974 Jun 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>