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

Diabetic nephropathy is characterized by persistent albuminuria, a decline in glomerular filtration rate (GFR) and elevated blood pressure. About 40% of all insulin-dependent diabetic patients will develop nephropathy, thus increasing their morbidity and mortality. The effect of early aggressive antihypertensive treatment with metoprolol, frusemide or thiazide in insulin-dependent diabetic patients with nephropathy has shown a significant reduction in albuminuria and in the rate of decline in the GFR (from 0.94 to 0.29 and 0.10 ml/min per month over 72 months of antihypertensive treatment). The effect of angiotensin converting enzyme (ACE) inhibition on kidney function in diabetic nephropathy showed that the GFR is not dependent on angiotensin II (Ang II), and that ACE inhibition diminished albuminuria, probably by lowering glomerular hypertension. In conclusion, antihypertensive treatment with ACE inhibitors or beta-blockers combined with a diuretic protects kidney function and reduces albuminuria in diabetic nephropathy. Angiotensin converting enzyme inhibitors can be considered as first-line drugs for hypertensive patients with diabetic nephropathy.
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PMID:The effect of beta-blockade and angiotensin converting enzyme inhibition on kidney function in diabetic nephropathy. 257 61

Investigators using intracerebroventricular (ICV) injections of competitive antagonists of angiotensin II (Ang II) to study thirst usually select doses sufficient to block drinking to IV Ang II. We questioned whether this test truly indicates the dose needed under physiological conditions when Ang II-induced hypertension, which inhibits thirst, is not present. Rats were prepared with chronic venous and ICV cannulas, plus femoral arterial cannulas in those used to measure arterial pressure. Captopril (100 mg/kg SC) was given before all experiments to block endogenous Ang II production. The test dose of Ang II, 50 ng/kg/min IV for 1 hr, increased water intake and arterial pressure. We selected an ICV dose of saralasin (Sar1Ala8Ang II), 4 micrograms bolus and 4 micrograms/hr for 75 min, that did not stimulate drinking itself and completely blocked drinking to IV Ang II. This dose of saralasin only partially (45%) reduced drinking to the same dose of Ang II IV when arterial pressure was lowered by giving the vasodilator diazoxide (15 mg/kg IV). Diazoxide itself did not stimulate drinking. These results support our concern that the criterion normally used to select ICV doses of Ang II antagonists probably underestimates the amount needed to inhibit angiotensinergic drinking in hypovolemic or hypotensive animals.
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PMID:Test of a criterion for selecting intracranial doses of angiotensin receptor blockers. 259 Aug 42

The aim of this study was to assess the effect of hypercalcaemia due to primary hyperparathyroidism on the pressor and aldosterone responses to angiotensin II (Ang II) infusion. Five patients with hyperparathyroidism were studied, before and after parathyroidectomy, and were compared with five normal subjects. After 30 min of equilibration, Asp1-Val5 Ang II was infused in all subjects at stepwise increasing dose rates of 2 and 4 ng/kg per min for 30 min each. In the hyperparathyroid patients the baseline levels of plasma parathyroid hormone and calcium were significantly higher than in the controls, and returned to normal after the parathyroidectomy; plasma aldosterone and renin activity were normal both before and after the parathyroidectomy. Two hyperparathyroid patients had high blood pressure levels, which were normalized after surgery. The increase in the aldosterone response from baseline at each time point of the Ang II infusion was greater in the hyperparathyroid patients before than after the operation (P less than 0.05), and greater than in the normals (P less than 0.05). No difference in the increased response of systolic or diastolic blood pressure was observed between the hyperparathyroid patients, either before or after the parathyroidectomy, and the normal subjects. High levels of extracellular calcium or parathyroid hormone, or both, might play a primary role in the aldosterone hyper-responsiveness to Ang II in the hyperparathyroid patients. The similar pressor response to Ang II in hyperparathyroid patients and the normal subjects suggests that hypercalcaemia does not potentiate the vasoconstrictive action of Ang II.
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PMID:Aldosterone and pressor responses to angiotensin II in primary hyperparathyroidism. 263 14

Plasma renin activity (PRA) suppression by angiotensin II (Ang II), the "short feedback loop," has been shown to be blunted in essential hypertension. Non-modulators comprise 50% of normal- and high-renin essential hypertensive individuals and are defined by their abnormal adrenal and renal responses to infused Ang II. This study sought to determine if the abnormal Ang II suppression of PRA in essential hypertension is specific to non-modulators. We measured PRA suppression during infusion of Ang II in 22 normotensive and 32 hypertensive (16 modulators and 16 non-modulators) subjects. A significant correlation between basal PRA and the fall in PRA in response to Ang II infusion was seen in the normotensives (r = -0.934, p less than 0.001) and modulators (r = -0.831, p less than 0.001) but not in the non-modulators (r = -0.275, p = 0.304). However, after 3 days of converting enzyme inhibition therapy, the correlation between basal PRA and decrement in PRA was significant in the non-modulators (r = -0.762, p less than 0.01). Thus, the abnormal PRA suppression documented previously in hypertensive individuals is a defect specific to non-modulators and is corrected with converting enzyme inhibition therapy.
Hypertension 1989 Jan
PMID:Angiotensin-mediated renin suppression is altered in non-modulating hypertension. 264 91

The potent and primate-selective renin inhibitor A-64662 (n = 8) or vehicle (n = 6) was administered intravenously for 7 days to sodium-depleted cynomolgus monkeys to investigate the chronic effects on arterial pressure, sodium excretion, and the renin-angiotensin-aldosterone system. A 0.1-mg/kg i.v. bolus followed by a continuous 0.01-mg/kg/min infusion of A-64662 lowered mean arterial pressure from 89 +/- 3 (average of 4 control days) to 75 +/- 4 mm Hg (p less than 0.05) after 1 day of administration. This decrement was associated with marked inhibition of plasma renin activity (PRA) from 57.7 +/- 11.1 to 1.3 +/- 0.6 ng angiotensin I (Ang I)/ml/hr (p less than 0.05). Similar hypotensive levels (range 73 +/- 4 to 77 +/- 4 mm Hg) were observed on days 2-7 of A-64662 infusion and PRA remained suppressed, ranging from 0.6 +/- 0.4 to 1.9 +/- 1.0 ng Ang I/ml/hr. Plasma angiotensin II (Ang II) levels were reduced (p less than 0.05) from the control value of 66.7 +/- 20.2 to 12.4 +/- 3.3 and 26.4 +/- 6.5 pg/ml on the second and seventh days, respectively, of A-64662 infusion. In contrast, infusion of vehicle alone had no discernible effect on mean arterial pressure, PRA, or plasma Ang II concentrations. Plasma aldosterone decreased (p less than 0.05) from control on the second and third days of A-64662 infusion, although differences between the treatment groups were not detected throughout the study. Urinary sodium excretion remained at control levels throughout the infusion of A-64662. Cessation of A-64662 administration resulted in a recovery of mean arterial pressure to preinfusion levels within 1 day. This study indicates that continuous infusion of A-64662 results in a sustained hypotension in sodium-depleted monkeys. This effect appears to be related, at least partially, to inhibition of PRA and lower plasma Ang II levels.
Hypertension 1989 Mar
PMID:Effects of chronic infusion of renin inhibitor A-64662 in sodium-depleted monkeys. 264 17

The direct effects of a renin inhibitor, N-acetyl-pepstatin and five angiotensin converting enzyme inhibitors, captopril and the active diacid forms of enalapril, ramipril, cilazapril, and CS-622, on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries. Vascular renin activity and angiotensin II (Ang II) released into the perfusate were determined. Infusion of N-acetyl-pepstatin (5 X 10(-8)-5 X 10(-6) M) suppressed vascular renin activity and Ang II release dose dependently. Isoproterenol (10(-6) M) induced a 135 +/- 30% increase in Ang II release from the basal value. N-Acetyl-pepstatin (5 X 10(-6) M) suppressed isoproterenol-induced Ang II release. Infusions of 5 X 10(-6) M captopril and the diacid forms of enalapril, ramipril, cilazapril, and CS-622 by themselves had little effect on Ang II release, but concomitant infusion of isoproterenol with these angiotensin converting enzyme inhibitors significantly decreased Ang II release (71 +/- 21%, 51 +/- 40%, 8 +/- 21%, 69 +/- 24%, and 44 +/- 29% increase, respectively, from the basal values). These results indicate that N-acetyl-pepstatin suppresses the vascular renin-angiotensin system. This effect may in part contribute to the hypotensive actions of renin inhibitors. Although angiotensin converting enzyme inhibitors also suppress locally generated Ang II, the mechanism and physiological significance still remain to be clarified.
Hypertension 1989 Jun
PMID:Renin inhibitor and converting enzyme inhibitors suppress vascular angiotensin II. 266 30

Pharmacological suppression of the renin angiotensin system (RAS) by inhibiting angiotensin-converting enzyme (ACE), both as monotherapy and in conjunction with other conventional agents, has been proven to be an effective therapeutic approach to the treatment of hypertension and congestive heart failure. Renin is the enzyme that catalyzes the first and rate limiting step, preceding the involvement of ACE, in the production of the potent pressor hormone angiotensin II (Ang II). Unlike ACE, which has multiple substrates, renin is selective for a single naturally occurring substrate, angiotensinogen. Interruption of the generation of ANG II by renin inhibitors at the highly specific, initial step of the cascade may have therapeutic advantages over ACE inhibitors and other antihypertensive agents with less precise mechanisms of action, by producing fewer clinical side effects. Exciting advances in the discovery of renin inhibitors have led to the synthesis of potent, dipeptide inhibitors of renin, which have been shown in the laboratory to be efficacious hypotensive agents when administered intravenously. Although there are recently reported compounds that demonstrate some degree of oral activity, efforts to enhance bioavailability are presently underway in order to develop orally active therapeutic agents. The development of renin inhibitors will provide target-specific agents for the treatment of various cardiovascular disorders, and will serve as invaluable tools to study the role of the RAS in regulating blood pressure and fluid volume. An overview of the progress in the discovery and development of renin inhibitors is presented.
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PMID:Renin inhibitors: discovery and development. An overview and perspective. 267 75

Pro-His-Pro-Phe-His-Statine-Ile-Phe-NH2 (R-Pep-27), a potent renin inhibitory peptide, was infused into the conscious, sodium-depleted Macaca fascicularis at doses of 0, 0.1, 1, 4, 16, and 32 micrograms/kg/min for 10 minutes. At all doses greater than 0.1 microgram/kg/min, there was a parallel decrease in mean arterial pressure (MAP), plasma renin activity, and plasma angiotensin II (Ang II) concentration. On the other hand, assays with monoclonal antibodies specific for total renin and active renin demonstrated that the peptide's inhibition of circulating active renin stimulated the release of both. The maximal effective R-Pep-27 dose was approximately 16 micrograms/kg/min, which reduced MAP by an average of 15.8 +/- 1.4 mm Hg (n = 14) and plasma renin activity and plasma Ang II concentration to 3% (n = 9) and 15% (n = 5), respectively, of the pretreatment values. At 0.1 microgram/kg/min, there was no significant decrease in MAP; however, measurement of plasma renin activity showed an average decrease in activity of 42% (n = 3). No significant change in the heart rate was observed at all the doses studied. For comparison, intravenous captopril (400 micrograms/kg bolus) was administered after the MAP of the monkeys had recovered from the peptide experiments, and it reduced MAP by 25.1 +/- 2.4 mm Hg (n = 10) without significantly changing plasma renin activity. As anticipated, injection of angiotensin I (80-160 ng/kg bolus) into sodium-depleted monkeys during peptide infusion caused a transient rise in MAP of 14.8 +/- 5.4 mm Hg (n = 4) above the mean pretreatment value.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1989 Nov
PMID:Effects of renin inhibition in the conscious primate Macaca fascicularis. 268 Sep 62

Hypertension is an important risk factor in the progression of renal failure, particularly in patients with pre-existing glomerulopathies such as diabetes and chronic glomerulonephritis. The mechanisms involved in hypertensive glomerular injury are currently unclear and cannot be studied in humans because of the constraints of human experimentation. However, recent animal studies have elucidated mechanisms which may explain the variable relationship between systemic hypertension and glomerular injury. Experimentally, at similar levels of systemic hypertension, glomerular injury only develops when preglomerular resistances are ineffective, thus allowing the development of glomerular hypertension. The mechanisms by which the haemodynamic stress of elevated intracapillary pressures and flows lead to progressive glomerular damage are at present unknown. Endothelial cell injury, increased mesangial traffic and/or trapping of macromolecules and epithelial cell injury appear to occur early, followed by in situ inflammatory and microthrombotic mechanisms. The intrarenal renin-angiotensin system appears to play an important role in the pathogenesis of progressive glomerular injury. Haemodynamically, angiotensin II (Ang II) has a relatively greater vasoconstrictive effect on efferent than on afferent arterioles. In addition, Ang II decreases the glomerular ultrafiltration coefficient. These combined effects result in increased intraglomerular capillary pressures. Angiotensin II increases the uptake and decreases the egress of circulating macromolecules in the glomerular mesangium and fosters mesangial cell mitogenesis. Thus, inhibition of Ang II generation may explain why angiotensin converting enzyme (ACE) inhibitors may be effective in arresting or slowing the progression of renal failure in experimental animals and in man.
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PMID:Possible mechanism for the renoprotective effect of angiotensin converting enzyme inhibitors. 269 55

Angiotensin II (Ang II) has been shown to cause hypertrophy of cultured quiescent rat aortic smooth muscle cells. This observation along with the recent demonstration of angiotensinogen messenger RNA (mRNA) in the vessel wall has led us to postulate a role for Ang II in hypertensive smooth muscle hypertrophy. One of the earliest responses in a wide variety of cells in response to a growth-promoting agent is the induction of the proto-oncogene c-fos. To investigate the mechanism of the action of Ang II, we investigated the effect of Ang II on the expression of the c-fos gene in rat aortic smooth muscle cells that were made quiescent by being grown in a defined serum-free media for 48 hours. Ang II (10(-6)-10(-10) M) resulted in a dose-dependent increase in c-fos mRNA expression. This induction was angiotensin-receptor specific since it was completely abolished by the competitive inhibitor saralasin. Inhibition of protein synthesis did not block the rise in c-fos mRNA expression; it resulted in a superinduction and stabilization of the c-fos mRNA. Using a nuclear runoff transcription assay, we demonstrated that Ang II stimulated the transcription rate of the c-fos gene. This activation of c-fos gene expression may be an important mechanism in the angiotensin-induced smooth muscle hypertrophy.
Hypertension 1989 Jun
PMID:Angiotensin II induces c-fos expression in smooth muscle via transcriptional control. 273 16


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