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)

The activities of the Na+--K+-ATPase, succinic dehydrogenase (SDH/, lactic dehydrogenase (LDH/ and glucose-6-phosphat dehydrogenase (G-6-PDH/ were studied in the cortex outer and inner medulla of the kidneys of rats with spontaneous hypertension (SHR) and were compared with those of control normotensive Wistar rats. The SHR aged 6--8 weeks had durint the prehypertensive and the early hypertensive stage the same enzymatic activities as control rats. Rats with a steady SH aged 16-22 weeks had low specific activity of the, Na+--K+-ATPase, SDH and LDH in the outer medulla. The latter can be associated with decreased intensity of the energy metabolism and a reduction of the active sodium transport in the ascending limb of the loop of Henle in the SHR rats and cold cause the phenomenon of exaggerated natriuresis characteristic of hypertension.
 ...
PMID:[Na+--K+-adenosine triphosphatase and some oxidoreductases in the kidney of rats with spontaneous hypertension]. 12 6

One of several novel peptidic inhibitors of angiotensin converting enzyme (CEI) has been studied intravenously both in normal male volunteers and severely hypertensive patients without any clinically significant adversity or intolerance. Hypertensive patients experienced a significant yet gradual reduction in resting arterial pressure without hypotension. The addition of a diuretic agent was observed to potentiate this antihypertensive effect. Normal, sodium replete volunteers received this nonapeptide intravenously in doses up to 2-0 mg/kg without any significant cardiovascular effect. Both patients and normal subjects exhibited reversible dose related increases in angiotensin I and renin levels after receiving the peptide. The plasma renin response to tilting was also potentiated by CEI. These findings suggest that intravenous CEI may be of value in the treatment of severely elevated hypertension and as a tool to evaluate vasoconstrictor and volume factors in hypertension.
 ...
PMID:Endocrine and cardiovascular consequences of angiotensin converting enzyme inhibition. 19 63

Serum angiotensin converting enzyme (ACE) activity and plasma renin activity (PRA) were studied during the development of the widespread necrotic arterial disease that occurs in the induction phase of one-kidney perinephritis hypertension. Control serum ACE activity was significantly higher in rabbits developing many arterial lesions than it was in rabbits developing relatively few arterial lesions. Serum ACE decreased 7 days after the production of unilateral perinephritis in all rabbits. Following contralateral nephrectomy, serum ACE decreased further in rabbits devloping many arterial lesions but returned toward control values in rabbits developing relatively few arterial lesions. Significant inverse correlations were demonstrated for the total number of arterial lesions that developed relative to a) the decrease in serum ACE activity 7 days after the production of unilateral perinephritis, b) the lowest or the average serum ACE activity during the period of development of the arterial lesions after contralateral nephrectomy, and c) the change in serum ACE activity during the period of development of the arterial lesions. Chronic treatment with SQ 20,881, a synthetic nonapeptide inhibitor of ACE activity, during the period of development of the hypertension and the arterial lesions significantly reduced the serum ACE activity and the hypertension but did not change interrelationships between serum ACE activity and the number of arterial lesions that developed. PRA significantly decreased after the production of perinephritis and decreased somewhat further during the induction period of the hypertension after contralateral nephrectomy. No relationships were demonstrated between PRA, or changes in PRA, and the development of arterial lesions. The increase in blood pressure during the incubation period of the hypertension did not correlate with the number of arterial lesions that developed. These finding indicate that serum ACE activity reflects importantly on the capacity to develop necrotic arterial lesions during the induction phase of one-kidney perinephritis hypertention and on functional events relating to their pathogenesis.
 ...
PMID:Serum angiotensin converting enzyme activity and the capacity to develop hypertention-associated arterial disease. Studies during the induction phase of one-kidney perinephritis hypertension in rabbits. 21 77

The effects of hydralazine (3 mg/kg) and the angiotensin I-converting enzyme (ACE) inhibitor captopril (SQ 14,225) (100 mg/kg) on mean arterial blood pressure, plasma renin activity, urinary volume and urinary Na+,K+, and aldosterone concentrations were examined in spontaneously hypertensive rats of the Okamoto and Aoki strain (SHR) after oral daily dosing for 2 weeks, 3 or 6 months. Captopril caused progressive cumulative reductions in blood pressure resulting in normalization of pressure after 6 months of dosing. Hydralazine also significantly reduced blood pressure but not to the level of normotensive rats of the Wistar-Kyoto strain (WKY). Reductions in heart size paralleled the changes in blood pressure, normalization of cardiac hypertrophy occurring after captopril but not hydralazine. Plasma renin activity increased approximately 2-3 fold after hydralazine and 15-fold after captopril. Neither hydralazine nor captopril had any consistent effects on 24-hr urine volume, urinary Na+,K+ or aldosterone excretion. These results indicate that chronic inhibition of ACE with captopril induces normalization of blood pressure in SHR, a normal-renin model of hypertension.
 ...
PMID:Effects of chronic treatment with captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats. 23

The short-term cardiovascular and endocrine effects of an orally active angiotensin converting enzyme inhibitor, SQ14,225, were evaluated in 17 subjects with drug-resistant hypertension (10 with essential and seven with renovascular hypertension). On normal dietary sodium, SQ14,225 (after 3 days at average dose of 664 mg/day) reduced mean arterial pressure (MAP) significantly (from 141 +/- 4 to 122 +/- 4 mm Hg, (SE), p less than 0.001). However, only eight of the patients achieved blood pressures within the normotensive range. Of eight patients with residual hypertension, seven exhibited further decreases in MAP (from 132 +/- 4 to 108 +/- 6 mm Hg (SE), p less than 0.001) when dietary sodium was reduced to 10 mEq/day. No rebound hypertension was noted when treatment was temporarily discontinued for 3 days in 11 patients. The reductions in blood pressure were not associated with either orthostatic hypotension or interference with baroreceptor reflexes. The values of supine plasma renin activity (PRA) were not always predictive of blood pressure responsiveness to the drug. With treatment, plasma aldosterone concentrations (PAC) decreased modestly (values from 40 +/- 9 to 22 +/- 3 ng/dl (SE), p less than 0.05). The plasma concentrations of cortisol, norepinephrine and serum potassium were left unchanged during the period of studies. The present study has not defined the exact mechanism by which SQ14,225 lowered blood pressure. Nevertheless, it indicates that this agent may be a practical therapeutic adjunct in the treatment of certain subsets of the human hypertensive population. The lack of serious interference with cardioscular and humoral homeostasis adds to its attractiveness as a therapeutic agent.
Hypertension
PMID:Converting enzyme inhibition with an orally active compound in hypertensive man. 23 90

Purified peptidyl dipeptidase (angiotensin I converting enzyme or kininase II) from human lung or hog kidney is inhibited by commercially prepared plasma protein preparations, by human serum albumin and by the additive albumin stabilizer, acetyltryptophan. After the initial steps of purification, albumin was detected by immunodiffusion as a component in human lung peptidyl dipeptidase preparation. Fragment C of albumin (sequence 124-298) is a more potent inhibitor than the parent molecule (Ki = 1.7 X 10(-5)M). Reduction and carboxymethylation of five of the six S-S bridges in Fragment C yield the most potent noncompetitive inhibitor (Ki = 3 X 10(-6)M). Reduction of the sixth bridge raises the K1. This indicates that maintenance of the tertiary structure in Fragment C is of importance for the inhibition. Neither albumin nor Fragment C are substrates of the enzyme. Fragment C and its derivative also inhibit the inactivation of bradykinin by the purified human enzyme and by the peptidyl dipeptidase on the surface of intact cultured human endothelial cells.
Hypertension
PMID:Inhibition of human peptidyl dipeptidase (angiotensin I converting enzyme: kininase II) by human serum albumin and its fragments. 23 85

1. The response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to inhibition of angiotensin I converting enzyme (kininase II) with captopril has been studied in patients with severe, treatment-resistant, malignant hypertension. 2. Nine patients with a past history of severe hypertension, supine diastolic blood pressure greater than 120 mmHg before conventional antihypertensive therapy and resistant to conventional antihypertensive therapy were studied. 3. Captopril administration resulted in a marked decrease in arterial blood pressure and plasma aldosterone concentration and an increase in plasma renin activity. 4. Although arterial blood pressure remained significantly below the values observed during the control period, pressure did tend to increase again after 3 days. Addition of hydrochlorothiazide kept arterial pressure significantly below pretreatment control values.
 ...
PMID:Response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to long-term administration of captopril in patients with severe, treatment-resistant malignant hypertension. 39 84

It has been suggested that intrarenal levels of angiotensin II may preferentially control efferent arteriolar resistance or may influence the glomerular filtration coefficient (Kf). To examine these possibilities, micropuncture and clearance experiments were performed on nine anesthetized dogs evaluating renal and glomerular hemodynamics before and during the administration of an angiotensin converting enzyme inhibitor (SQ20,881). During the micropuncture measurements, renal arterial pressure was reduced to range of 85 to 90 mm Hg in order to maximize renin secretion and intrarenal formation of angiotensin II. Also, this procedure minimizes potential errors in the determination of single nephron glomerular filtration rate (SNGFR) and of glomerular pressure when estimated by techniques that require complete blockade of proximal tubule fluid flow. During the administration of SQ20,881, a converting enzyme inhibitor (CEI), renal blood flow increased significantly by 13%, but GFR was not altered. There were no significant alterations in SNGFR, proximal tubule pressure, peritubular capillary pressure or estimated glomerular pressure. By using the micropressure measurements in combination with the whole kidney hemodynamic data, it was estimated that afferent resistance was reduced 23%. Although significant decreases in efferent resistance could not be documented, there was a tendency for this variable to decrease also. Neither Kf nor effective filtration pressure were altered significantly by CEI. These results do not support the contention that intrarenal effects of angiotensin II are exerted predominantly on the efferent arteriolar resistance segments; rather, they suggest that angiotensin may exert a modest tonic effect on both pre- and postglomerular resistance elements in the anesthetized hydropenic dog.
Hypertension
PMID:Glomerular and renal hemodynamics during converting enzyme inhibition (SQ20,881) in the dog. 39 40

We assessed the role of the renin-angiotensin system in the response of the renal circulation to restriction of sodium intake in 38 normal patients. Both saralasin (10 to 30 ng/kg/min), an angiotensin antagonist, and SQ 20881 (30 to 300microgram/kg), a converting enzyme inhibitor, induced a dose-related increase in renal blood flow (xenon 133 washout) only when the resin-angiotension system was activated by restriction of sodium intake to 10 MEq/day. Increasing doses of saralasin (100 to 1,000 ng/kg/min) reduced renal blood flow, presumably due to the angiotensin-like action of this partial agonist. The renal vascular response to SQ 20881 paralleled the endocrine response: An identical threshold dose (30 microgram/kg) increased renal blood flow and reduced plasma angiotensin II concentration, which fell despite a progressive rise of plasma renin activity. Plasma bradykinin concentration did not change in response to SQ 20881, which also blocks kininase II. Both agents also induced a small but consistent and statistically significant reduction in arterial blood pressure, which will be important in assessing the pathogenetic significance of a blood pressure reduction in patients with hypertension. This study indicates that angiotensin mediates the renal vascular response to restriction of salt intake in normal man and provides an approach to assessing the role played by angiotensin in the pathogenesis of functional renal disease.
 ...
PMID:Renal vascular response to interruption of the renin-angiotensin system in normal man. 59 39

Patients with essential arterial hypertension demonstrate abnormal vasodilator capacity either during increased cardiac metabolic demand or during pharmacological vasodilation. Structural and functional damage to the coronary microcirculation has been proposed as one of the major causes of impaired coronary reserve in this disease. To assess the role of microvascular impairment in regional myocardial blood flow (MBF), 27 patients with essential hypertension were evaluated by dynamic positron emission tomography (PET) at rest, during atrial pacing and after dipyridamole infusion and compared with 13 healthy subjects. All patients had normal coronary arteries, 17 had moderate to severe hypertension and 10 had mild hypertension. Baseline mean MBF of 0.97 +/- 0.25 ml/min/g was significantly increased to 1.60 +/- 0.38 during atrial pacing and 2.35 +/- 0.95 after dipyridamole infusion (p < 0.01); however, mean flow during atrial pacing and after dipyridamole infusion was significantly lower than in healthy subjects (2.15 +/- 0.73 and 3.71 +/- 0.86 ml/min/g, p < 0.05 and p < 0.01, respectively). The MBF response to atrial pacing and dipyridamole infusion was similarly depressed in patients with mild and severe hypertension. The study was repeated after 6 months of antihypertensive treatment with the calcium antagonist verapamil or the angiotensin converting enzyme (ACE) inhibitor enalapril in a subgroup of 20 patients as part of a randomised, single-blind clinical trial. This study is still in progress; the initial 16 patients treated with verapamil or enalapril showed an obvious improvement in MBF values during atrial pacing and after dipyridamole infusion after 6 months of therapy (mean MBF: 2.10 +/- 0.64 and 2.99 +/- 1.63 ml/min/g, respectively, p < 0.05 vs pretreatment values). In conclusion, obvious impairment of MBF during atrial pacing and after dipyridamole infusion was observed in hypertensive patients with normal coronary arteries and this appeared unrelated to the severity of hypertension. Therapy with verapamil or enalapril improved coronary reserve and MBF response to an increase in myocardial oxygen demand.
 ...
PMID:Regional myocardial blood flow and coronary reserve in hypertensive patients. The effect of therapy. 128 84


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