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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A significant factor in the management of hypertension is the extent to which patients comply with the treatment regimen. A retrospective analysis was undertaken to determine the relationship between antihypertensive formulation, regimen compliance, and the utilization of health care services. Data for this analysis were derived from the state of South Carolina's Medicaid computer archive. The study population consisted of 1000 randomly selected patients initially prescribed one of the following antihypertensive regimens as monotherapy: atenolol once daily, captopril BID, oral clonidine BID, transdermal clonidine once weekly, diltiazem BID, enalapril BID, metoprolol BID, prazosin BID, terazosin once daily, and sustained-release verapamil once daily. Multivariate regression analysis was used to determine the incremental influence of selected demographic characteristics, use of medical services before diagnosis of hypertension, initial antihypertensive medication, medication possession ratio for antihypertensive therapy, and number of maintenance medications for diseases other than hypertension on post-period health care expenditures. The results indicated that patients initially prescribed antihypertensive medication requiring once-daily or once-weekly administration experienced an increased utilization of antihypertensive medication, needed fewer changes in their therapeutic regimen, and far less need for concomitant therapy for blood pressure control compared with those prescribed a BID regimen. Patients in the once-daily or once-weekly groups also used significantly fewer physician, hospital, and laboratory services (P < or = 0.05).
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PMID:Effect of pharmaceutical formulation for antihypertensive therapy on health service utilization. 822 22

Morbidity from wound healing was retrospectively analyzed in a series of 202 consecutive patients with tumors of the soft tissue of the extremities, torso and head and neck region who were treated with preoperative irradiation and conservative operation at the Massachusetts General Hospital between January 1971 and June 1989. A radiation boost dose was given to 143 patients (71 percent) postoperatively. The overall wound complication rate was 37 percent. One patient died because of necrotizing fasciitis. In 33 instances (16.5 percent), secondary operation was necessary, including six patients (3 percent) who required amputation. The wounds in the remaining 40 patients (20 percent) were treated without operation. Multivariate analyses of the data showed the factors that were significantly associated with wound morbidity: tumor in the lower extremity (p < 0.001), increasing age (p = 0.004) and postoperative boost with interstitial implant (p = 0.016). Accelerated fractionation (BID, two fractions per day) reached borderline statistical significance (p = 0.074). Two other factors showed association with wound morbidity by univariate analysis, but not in multivariate model: high pathologic grade (p = 0.02) and estimated volume of resected specimen > or = 200 milliliters (p = 0.065). Patient gender, intercurrent disease (diabetes or hypertension), obesity, maximal tumor size, primary versus recurrent tumor, duration of bed rest postoperatively, dose of postoperative boost radiation, the use of postoperative boost, the use of adjuvant chemotherapy and year of treatment did not show significant importance for wound morbidity. When the severe wound complications (defined as requiring secondary operation and including the patient who died because of necrotizing fasciitis) were considered, among all analyzed variables, only localization of tumor in the lower extremity as a single factor was significant (p < 0.001). Techniques for managing the wound are considered which are judged likely to contribute to a decrease of the incidence of wound healing delays.
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PMID:Wound healing after preoperative radiation for sarcoma of soft tissues. 842 99

The aim of this work was to test whether calcium channel blockers interfere with skin vasoconstrictor reflexes that minimize postural increases in capillary pressure and avoid fluid extravasation and eventually subcutaneous edema. Studies were conducted in 23 untreated mild to moderate essential hypertensives; drugs, either calcium channel blockers or not, were given for 2 weeks according to a crossover, sequence-randomized design. Skin blood flow was measured by laser Doppler flowmetry in two skin areas: (1) the dorsum of the foot, where arteriovenous anastomoses are poorly represented, and (2) the plantar surface of the great toe, where those anastomoses are predominant. Determinations were obtained both with the foot at heart level and with it placed passively 50 cm below the heart level; percent flow changes from the horizontal to the dependent position were the measure of postural vasoconstriction. Two dihydropyridine derivatives, amlodipine (10 mg UID) and nifedipine (60 mg UID), and verapamil (240 mg BID), a chemically unrelated compound, diminished to similar extents the postural fall in skin blood flow at the dorsum of the foot. Blockade of alpha1-adrenergic and AT-1 subtype angiotensin II receptors by doxazosin (4 mg UID) and losartan (50 mg UID), respectively, exerted no effect. Postural skin blood flow responses at the plantar surface of the great toe were unmodified during the pharmacological trials. Thus, calcium channel blockers of different chemical origins antagonized postural skin vasoconstriction at the dorsum of the foot. The data indicate altered postural capillary blood flow regulation, since arteriovenous anastomoses are anatomically absent at this site; the effect was independent of either alpha1-adrenoceptor or angiotensin II receptor antagonism. Interference with skin postural vasoconstrictor mechanisms may result in net filtration of fluid to the extravascular compartment. This mechanism might explain the as yet unknown pathogenesis of ankle edema during treatment with calcium antagonists.
Hypertension 1997 Mar
PMID:Calcium channel blockers blunt postural cutaneous vasoconstriction in hypertensive patients. 905 91

The potential role of endothelin-1 (ET-1) in essential hypertension in humans is still subject to debate. We recently reported strong sodium retention and renal vasoconstriction during pathophysiological increments in plasma ET-1. Apart from this vasoconstrictor action, ET-1 also has mitogenic properties that play a role in the pathophysiology of hypertension. On the other hand, some data refute an important role of ET-1 in hypertension. We therefore investigated in nine subjects with essential hypertension the constrictor actions of ET-1 by challenging these subjects with a systemic infusion of ET-1 (0.5 ng/kg per minute for 60 minutes, then 1.0 ng/kg per minute for 60 minutes, and finally 2.0 ng/kg per minute for 60 minutes). Furthermore, we studied whether these effects of ET-1 could be modulated by oral use of the angiotensin-converting enzyme inhibitor enalapril (20 mg BID) or the calcium channel blocker nifedipine (60 mg OD). ET-1 infusion increased plasma ET-1 levels from 2.5+/-0.4 to 11.6+/-1.0 pmol/L (P<.05). Blood pressure rose by approximately 10 mm Hg (P<.05). Cardiac index decreased by 21+/-22%, whereas calculated systemic vascular resistance increased by 27+/-6% (P<.05). Renal blood flow decreased from 1051+/-94 to 707+/-60 mL/min at the end of the ET-1 infusion (P<.05), and calculated renal vascular resistance increased from 118+/-19 to 189+/-19 mm Hg x min/L (P<.05). Sodium excretion decreased from 227+/-39 to 111+/-15 micromol/min (P<.05). Both enalapril and nifedipine treatment prevented the systemic effects of ET-1 infusion in these subjects. However, during enalapril treatment, despite renal predilatation, ET-1 reduced renal blood flow (from 1119+/-132 to 701+/-75 mL/min, P<.05) and increased renal vascular resistance (from 111+/-16 to 187+/-28 mm Hg x min/L, P<.05) to the same levels as during ET-1 infusion alone. Nifedipine pretreatment attenuated the ET-1-induced fall in renal blood flow (from 1088+/-93 to 907+/-68 mL/min) and increase in renal vascular resistance (from 105+/-9 to 133+/-10 mm Hg x min/L). Although neither drug modulated the antinatriuretic effect of ET-1, nifedipine increased basal sodium excretion (P<.05), which compensated for the decrease during ET-1 infusion. In conclusion, essential hypertensive subjects are sensitive to the vasoconstrictor effects of ET-1. Both enalapril and nifedipine can prevent the systemic effects of ET-1, but nifedipine seems more effective in attenuating the renal constrictor effects of ET-1.
Hypertension 1997 Jul
PMID:Endothelin-1-induced vasopressor responses in essential hypertension. 946 Dec 48

Since salt intake may affect blood pressure response to antihypertensive drugs, an individual's salt-sensitivity status may be an important consideration in the selection of a medication. The purpose of this single-blind study was to assess the impact of salt sensitivity on the antihypertensive effects of isradipine. A total of 21 evaluable hypertensive patients (10 white, 11 black) 35 to 73 years of age (mean 55.9 years) were randomized to a low-salt diet (mean 24-hour urine sodium 100+/-14 mmol) or a high-salt diet (mean 24-hour urine sodium 210+/-22 mmol) for 7 weeks, followed by crossover to the other diet after a 2-week washout period. On each diet regimen, patients received placebo for 2 weeks, followed by optimal titration of isradipine (2.5 to 10 mg BID) for blood pressure control during the last 5 weeks. On the high-salt diet, salt-sensitive hypertensives (mean arterial blood pressure increase > or = 5 mm Hg, n=5) exhibited a systolic/diastolic blood pressure change of -18.7/-19.6 mm Hg from 157.2/102.9 mm Hg after 5 weeks of isradipine treatment, whereas on a low-salt diet, blood pressure change was -6.9/-12.0 mm Hg from 148.7/97.3 mm Hg. Non-salt-sensitive patients (n=16) exhibited a systolic/diastolic blood pressure change of -12.6/-7.6 mm Hg from 155.3/98.6 mm Hg on the high-salt diet and -19.2/-10.9 mm Hg from 161.0/102.6 mm Hg on the low-salt diet after treatment with isradipine. The absolute blood pressure attained in both salt-sensitive and non-salt-sensitive patients was almost identical with isradipine therapy despite variation in dietary salt, although slightly higher doses of isradipine were required in the salt-sensitive group. Consequently, isradipine, and perhaps calcium antagonists in general, manifests a more robust blood pressure-lowering effect in the setting of high sodium intake. This effect does, however, appear to be largely confined to individuals who are salt sensitive.
Hypertension 1997 Sep
PMID:Salt and blood pressure responses to calcium antagonism in hypertensive patients. 931 27

Surgical ablation of renal mass leads to a reduction in kidney function and commonly to the development of hypertension and chronic renal failure (CRF) in rats. The objective of this study was to determine whether endothelin (ET)-1 is involved in the maintenance of the hypertension that accompanies loss of renal mass. First, we demonstrated the antihypertensive efficacy of PD 155080, a selective, orally active ET(A) receptor antagonist, in a group of rats made hypertensive by continuous intravenous infusion of ET-1 (2.5 pmol x kg(-1) x min[-1]) for 7 days. ET-1 produced a sustained hypertension and PD 155080 (56.4 micromol/kg [25mg/kg] BID PO) normalized blood pressure (BP) during the 5 days of drug administration. In a second experiment, Sprague-Dawley rats underwent a 5/6 reduction in renal mass (RRM); 4 weeks later, PD 155080 administered for 7 days resulted in a sustained reduction in BP. Sham-operated rats also showed a slight hypotensive response to PD 155080 administration. Plasma urea nitrogen, plasma creatinine, urinary protein excretion, and creatinine clearance were not altered by PD 155080 administration in RRM or sham rats. In a third experiment, we investigated the contribution of the renin-angiotensin system to BP control in RRM rats given PD 155080. In these rats, PD 155080 reduced BP during 5 treatment days, and this antihypertensive effect was not altered by coadministration of the angiotensin-converting enzyme inhibitor enalapril in the drinking water (508 micromol/L [250 mg/L]). These results demonstrate that (1) ET-1 plays a role in established RRM hypertension through activation of the ET(A) receptor subtype, (2) lowering blood pressure with PD 155080 in RRM rats does not adversely affect renal function, and 3) the antihypertensive effect of ET(A) receptor antagonism is not opposed by the renin-angiotensin system.
Hypertension 1997 Dec
PMID:Role of endothelin in hypertension of experimental chronic renal failure. 940 86

In patients with congestive heart failure (CHF) receiving therapy with angiotensin-converting enzyme (ACE) inhibition, institution of calcium channel antagonism with amlodipine provided favorable effects. The goal of the present study was to define potential mechanisms for these effects by measuring left ventricular function, hemodynamics, and neurohormonal system activity in a model of CHF in which amlodipine treatment had been instituted either as a monotherapy or in combination with ACE inhibition. Thirty-two pigs were instrumented to allow measurement of cardiac index, total systemic resistance index, and neurohormonal activity in the conscious state and assigned to one of four groups: (1) rapid atrial pacing (240 bpm) for 3 weeks (n = 8), (2) amlodipine (1.5 mg x kg(-1) x d[-1]) and pacing (n = 8), (3) ACE inhibition (fosinopril 1.0 mg/kg BID) and pacing (n = 8), and (4) amlodipine and ACE inhibition (1.0 mg x kg(-1) x d(-1) and 1.0 mg/kg BID, respectively) and pacing (n = 8). Measurements were obtained in the normal control state and after the completion of the treatment protocols. With rapid pacing, basal resting cardiac index was reduced compared with control values (2.7+/-0.2 versus 4.7+/-0.1 L x min(-1) x m(-2), respectively, P<.05) and increased from rapid pacing-only values with either amlodipine or combination therapy (3.7+/-0.3 and 4.4+/-0.5 L x min(-1) x m(-2), respectively, P<.05). Basal resting total systemic resistance index was higher in the rapid pacing-only group compared with control values (2731+/-263 versus 1721+/-53 dyne x s x cm(-5) x m2, respectively, P<.05), was reduced with either amlodipine treatment or ACE inhibition (2125+/-226 and 2379+/-222 dyne x s x cm(-5) x m2, respectively, P<.05), and was normalized with combination therapy. Plasma catecholamines, renin activity, and endothelin levels were increased threefold with rapid pacing. Amlodipine, either as a monotherapy or in combination with ACE inhibition, did not result in increased plasma catecholamines and renin activity compared with the rapid pacing-only group. Furthermore, combination therapy reduced steady state norepinephrine and normalized epinephrine levels. The results of the present study demonstrated that monotherapy with either amlodipine or ACE inhibition provides beneficial effects in this pacing model of CHF. Combined amlodipine and ACE inhibition provided greater benefit with respect to vascular resistance properties and neurohormonal system activity compared with either monotherapy.
Hypertension 1998 Mar
PMID:Amlodipine monotherapy, angiotensin-converting enzyme inhibition, and combination therapy with pacing-induced heart failure. 949 58

Dietary salt restriction is a recommended adjunct with antihypertensive therapy. There may be racial differences in blood pressure response to salt restriction while on antihypertensive therapy. We performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (black, n=96; Hispanic, n=63; white, n=232). Participants were initially preselected for stage I to III hypertension and then further selected for salt sensitivity (> or = 5 mm Hg increase in diastolic blood pressure after 3 weeks of low salt [< or = 88 mmol/d Na+] and high salt [>190 mmol/d Na+] diet). We compared the antihypertensive effect of an angiotensin-converting enzyme inhibitor (enalapril 5 or 20 mg BID) or a calcium channel antagonist (isradipine 5 or 10 mg BID) during alternating periods of high and low salt intake. The main outcome measure was blood pressure change and absolute blood pressure level achieved with therapy. During the high salt diet (314.7+/-107.5 mmol/d urinary Na+) there was greater downward change in blood pressure with both enalapril and isradipine compared with the low salt diet (90.1+/-50.8 mmol/d Na+); however, the absolute blood pressure achieved in all races was consistently lower on a low salt diet for both agents. Black, white, and Hispanic isradipine-treated salt-sensitive hypertensives demonstrated a smaller difference between high and low salt diets (black, -3.6/-1.6 mmHg; white, -6.2/-3.9 mmHg; Hispanic, -8.1/-5.3 mm Hg) than did enalapril-treated patients (black, -9.0/-5.3 mm Hg; white, -11.8/-7.0 mm Hg; Hispanic, -11.1/-5.6 mm Hg). On the low salt diet, blacks, whites, and Hispanics had similar blood pressure control with enalapril and isradipine. On the high salt diet, blacks had better blood pressure control with isradipine than with enalapril, whereas there was no difference in the blood pressure control in whites and Hispanics treated with either drug. Dietary salt reduction helps reduce blood pressure in salt-sensitive hypertensive blacks, whites, and Hispanics treated with enalapril or isradipine. These data demonstrate that controlling for salt sensitivity diminishes race-related differences in antihypertensive activity.
Hypertension 1998 May
PMID:Influence of race and dietary salt on the antihypertensive efficacy of an angiotensin-converting enzyme inhibitor or a calcium channel antagonist in salt-sensitive hypertensives. 957 19

The structural and mechanical properties of small arteries are altered in rat models of hypertension. The precise role of humoral factors in these changes has not been determined. In deoxycorticosterone acetate (DOCA) salt hypertension, endothelin-1 (ET-1) peptide content and gene expression are enhanced in mesenteric resistance arteries. These vessels also present augmented vasoconstrictor responsiveness to vasopressin versus control uninephrectomized rats. To determine whether an interaction exists between vasopressin and ET-1 in the pathogenesis of small-artery structural alterations in DOCA-salt rats, we examined the effect of chronic V1 vasopressin receptor antagonism (OPC-21268, 30 mg/kg BID) on the structure and mechanical properties of mesenteric resistance arteries using a pressure myograph and the effect on preproendothelin-1 (preproET-1) gene expression, determined by Northern blot analysis of preproET-1 mRNA. Tail-cuff systolic pressures were elevated in DOCA-salt (200+/-11 mm Hg) versus uninephrectomized rats (109+/-4 mm Hg) and decreased slightly but significantly by OPC-21268 to 187+/-7 mm Hg (P<0.01). Treatment with DOCA-salt increased vascular media-lumen ratios and media cross-sectional areas and reduced both stress and incremental elastic modulus for a given pressure. However, there was no change in distensibility or incremental elastic modulus versus media stress. OPC-21268 partially attenuated the vascular growth in DOCA-salt rats. PreproET-1 mRNA was increased 2-fold in mesenteric arteries of DOCA-salt rats versus uninephrectomized rats, an effect abrogated by OPC-21268. Thus, DOCA-salt hypertension is associated with altered morphology of the small-arterial wall, without altering stiffness of the arterial wall components. OPC-21268 regressed in part these changes, suggesting the involvement of vasopressin. The concomitant attenuation of enhanced ET-1 expression by OPC-21268 suggests that ET-1 may be involved in mediating in part the vascular effects of vasopressin in DOCA-salt hypertensive rats.
Hypertension 1998 Oct
PMID:Effect of vasopressin antagonism on structure and mechanics of small arteries and vascular expression of endothelin-1 in deoxycorticosterone acetate salt hypertensive rats. 977 78

It has been suggested that combined inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) may lower blood pressure more effectively than either treatment alone, independent of the degree of salt and volume status or the activity of the renin-angiotensin system. The effects of NEP inhibition in hypertension associated with diabetes mellitus are largely unknown. We therefore compared ACE inhibition, NEP inhibition, and dual NEP/ACE inhibition in diabetic hypertensive rats. Spontaneously hypertensive rats (SHR) aged 9 to 10 weeks were injected with either streptozotocin (45 mg/kg) or citrate buffer and randomized to receive either the ACE inhibitor captopril (25 mg/kg BID), the NEP inhibitor SCH 42495 (30 mg/kg BID), the dual NEP/ACE inhibitor S 21402 (25 or 50 mg/kg BID), or vehicle by gavage for 4 weeks. A group of diabetic SHR was also allocated to receive the combination of SCH 42495 (30 mg/kg BID) and captopril (25 mg/kg BID). The degree of renal NEP inhibition was determined by autoradiography, and plasma renin activity (PRA) was determined by radioimmunoassay. In diabetic SHR, the dual NEP/ACE inhibitor (50 mg/kg BID), as well as the combination of the NEP inhibitor and the ACE inhibitor, reduced systolic blood pressure more effectively than the ACE inhibitor (P<0.001) or the NEP inhibitor (P<0.001) alone. In nondiabetic SHR, the dual NEP/ACE inhibitor and the ACE inhibitor were equally effective, while the NEP inhibitor had only slight blood pressure lowering effects. Relative heart weight decreased in parallel to the changes in blood pressure. Renal NEP was clearly inhibited (70% to 92%; P<0.001) by both the NEP inhibitor and the dual NEP/ACE inhibitor. Both the ACE inhibitor and the dual NEP/ACE inhibitor increased PRA, but the stimulating effect of dual NEP/ACE inhibition on PRA was less than that observed with ACE inhibition alone (P<0.05). Albuminuria in diabetic SHR was lower during treatment with both the dual NEP/ACE inhibitor (50 mg/kg BID) and the combination of NEP inhibition and ACE inhibition compared with vehicle treatment (P<0.05). In conclusion, the present study shows that hypertension in SHR with streptozotocin-induced diabetes is modulated by natriuretic peptides and thus is sensitive to NEP inhibition. The increased efficacy of dual NEP/ACE inhibition on blood pressure in diabetic SHR, compared with ACE or NEP inhibition alone, suggests that this therapeutic approach may prove beneficial in the treatment of hypertension associated with diabetes mellitus and other forms of volume-dependent hypertension.
Hypertension 1998 Oct
PMID:Dual inhibition of neutral endopeptidase and angiotensin-converting enzyme in rats with hypertension and diabetes mellitus. 977 79


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