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

It is now clear that specific angiotensin-dependent mechanisms contribute importantly to the pathophysiology of hypertension (HT) and altered renal function in models of two-kidney, one-clip (2-K, 1-C) HT in rats. The discovery of specific antagonists for angiotensin-converting enzyme and the newer angiotensin receptor and kinin receptor antagonists have allowed delineation of the contributions of these hormones to altered renal function in these models. The focus of interest in most of these studies has been the nonclipped kidney, which would be expected to ameliorate elevated blood pressure by exhibiting a pressure diuresis and natriuresis in the environment of systemic HT. Antagonism of the renin-angiotensin system in rat models of renal vascular HT indicates that the effects of angiotensin attenuate renal hemodynamic and excretory behavior, particularly in the nonclipped kidney. Furthermore, angiotensin attenuates the efficiency of autoregulation of renal hemodynamics in the nonclipped kidney. Function of the clipped kidney appears to be both angiotensin and perfusion pressure dependent. Evidence that inhibition of angiotensin reverses or improves these altered hemodynamic and excretory functions indicates that angiotensin may contribute importantly to the pathophysiology of HT in these models by altering or impairing the ability of the nonclipped or "normal" kidney to excrete sodium and volume. The precise roles of altered activity of vasodilator hormones to contribute to these alterations of renal function remains to be defined.
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PMID:Pathophysiology of altered renal function in renal vascular hypertension. 794 24

Clinical observations demonstrate an enhanced risk for myocardial infarction in patients with sustained activation of the local and/or systemic renin-angiotensin system, such as a high renin-sodium profile or a heritably enhanced expression of angiotensin converting enzyme. Chronic renin-angiotensin system blockade by angiotensin converting enzyme inhibition in patients with moderate heart failure reduces the rate of myocardial infarction and reinfarction. Preliminary experimental evidence suggests that these clinical observations may be partially explained by a proatherogenic effect of an activated renin-angiotensin system, which can downregulate the endothelial releasability of nitric oxide. Nitric oxide exerts many potentially antiatherogenic effects on endothelium, platelets and low density lipoproteins and indirectly on monocytes and leukocytes. Hypertension-induced chronic distension of elastic arteries upregulates the local renin-angiotensin system in these arteries and thereby downregulates nitric oxide releasability. Enhanced local synthesis of the trophic factor angiotensin-II and reduced releasability of the antitrophic factor nitric oxide appear to cooperate in the trophic adaptation of the distended vessel wall to the enhanced load, but with the disadvantage of enhanced susceptibility for atheroma development due to reduced releasability of nitric oxide. Chronic blockade of the renin angiotensin system by angiotensin converting enzyme inhibitors or by angiotensin receptor type-1 antagonists normalizes a reduced endothelial releasability of nitric oxide in several models, partially by a bradykinin-dependent mechanism. This endothelial protection proved to attenuate the progression of atherosclerosis in experimental models. The antiatherogenic potential of renin angiotensin system blockade in humans is presently under study.
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PMID:Vascular renin-angiotensin-system, endothelial function and atherosclerosis? 794 78

Renal artery stenosis, particularly related to advancing atherosclerotic disease, is a common concern to internists seeing patients with worsening hypertension and deteriorating renal function. Understanding the hormonal and hemodynamic consequences of critical vascular lesions allows better selection of antihypertensive therapy. With the application of potent antihypertensive agents--especially those that block the renin-angiotensin system, such as ACE inhibitors or the soon-to-be-released angiotensin receptor antagonists--blood pressure control often is not the primary reason to consider renal revascularization. Instead, protection of renal function beyond a critical level of arterial stenosis is becoming the main indication for both percutaneous angioplasty and surgical revascularization. Both procedures pose hazards, so optimal management of the patient with renovascular hypertension depends on achieving a balance between the risks and benefits to the individual patient. It remains incumbent upon the internist to weigh the cardiovascular and cerebrovascular risks against both the gains in blood pressure control and the likely progression of renal compromise during the patient's lifetime. Improved understanding of the outcomes of medical therapy versus revascularization depends on future prospective studies.
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PMID:Renovascular hypertension. 807 Apr 20

We examined the effects of angiotensin II (Ang II) and Ang-(1-7) on the release of [3H]norepinephrine elicited by nerve stimulation (2 Hz, 0.5 millisecond, for 2 minutes) in rat atria isolated with their cardioaccelerans nerves. The stimulation-induced release of [3H]norepinephrine was increased 50% by 3 x 10(-8) mol/L of either peptide. No further increase in [3H]norepinephrine release was observed with peptide concentrations up to 3 x 10(-7) mol/L. This effect was completely blocked by the nonselective angiotensin receptor antagonist saralasin (1 x 10(-7) mol/L). The type 1 angiotensin receptor antagonist DuP 753 (1 x 10(-6) mol/L) entirely prevented the increases in [3H]norepinephrine caused by Ang II and Ang-(1-7). On the other hand, the type 2 angiotensin receptor antagonist PD 123319 (1 x 10(-6) mol/L) prevented the increase in [3H]norepinephrine release elicited by Ang-(1-7) but not by Ang II. These results suggest that Ang-(1-7), like Ang II, could have a neuromodulatory function in rat atria via activation of specific angiotensin receptor subtypes, which could be the subtype 1 angiotensin receptor for Ang II and subtypes 1 and 2 for Ang-(1-7).
Hypertension 1994 Oct
PMID:Effects of angiotensin II and angiotensin-(1-7) on the release of [3H]norepinephrine from rat atria. 808 11

The past decade has been considerable advances in basic knowledge of the renin-angiotensin system. Perhaps the most important new development has been the appreciation of a tissue-based renin-angiotensin system that can be independently regulated from the circulation. Greater insight into the mechanism by which the renin-angiotensin system exerts its actions has been achieved through the study of molecular biology and pharmacologic characterization of multiple angiotensin receptor subtypes. Ang II is now considered a growth promoter in cardiovascular tissues, and the resultant vascular hypertrophy is an important contributor to the maintenance of hypertension. Ang II also plays a role in the kidney, not only as a regulator of hemodynamics, but in the development of structural changes (hypertrophy, sclerosis), which are important in the pathogenesis of a variety of renal disorders. Finally, a central role for the renin-angiotensin system in experimental renovascular hypertension has been reaffirmed. In the future, basic knowledge and techniques of investigation gained from experimental models will be used to investigate clinical disorders such as hypertension and various renal disorders characterized by abnormal function of the renin-angiotensin system.
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PMID:The renin-angiotensin system. New concepts in regulation of blood pressure and renal function. 817 86

An enhanced risk for myocardial infarction has been observed in humans with sustained activation of the local and/or systemic renin-angiotensin system, such as a high renin-sodium profile or a heritably enhanced expression of angiotensin converting enzyme. Chronic renin-angiotensin system blockade by angiotensin converting enzyme inhibition reduces the rate of myocardial reinfarction in patients with moderate heart failure. Preliminary experimental evidence suggests that these clinical observations may be partially explained by a proatherogenic effect of an activated renin-angiotensin system, which can downregulate the expression of the endothelial nitric oxide synthase III. Nitric oxide exerts many potentially antiatherogenic effects on endothelium, platelets and low density lipoproteins and indirectly on monocytes and leukocytes Hypertension-induced chronic distension of elastic arteries upregulates the local renin-angiotensin system in these arteries and thereby downregulates nitric oxide synthase. Enhanced local synthesis of the trophic factor angiotensin-II and reduced releasability of the antitrophic factor nitric oxide appear to cooperate in the trophic adaptation of the distended vessel wall to the enhanced load, but with the disadvantage of enhanced susceptibility for atheroma development due to reduced availability of nitric oxide. Chronic blockade of the renin-angiotensin system by angiotensin converting enzyme inhibitors or by angiotensin receptor type-1 antagonists normalizes a reduced endothelial nitric oxide availability in several models, partially by a bradykinin-dependent mechanism. This endothelial protection proved to attenuate the progression of atherosclerosis in experimental models. The antiatherogenic potential of renin-angiotensin system blockade in humans is presently under study.
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PMID:The endothelium and the renin-angiotensin system. 818 13

Chronic angiotensin-converting enzyme (ACE) inhibition prevents endothelial dysfunction in hypertension and hypercholesterolemia. Long-term treatment with cyclosporin A impairs endothelium-dependent relaxations and augments contractions to angiotensin II in the rat aorta. The present study compares vasomotor responses to several vasoconstrictor and dilator stimuli after 6 weeks of oral treatment with either the angiotensin-converting enzyme inhibitor lisinopril (10 mg/kg per day), the angiotensin subtype 1 receptor antagonist D 8731 (10 mg/kg per day), cyclosporin A (15 mg/kg per day), or a combination of cyclosporin A with lisinopril or D 8731 (n = 15 rats per group). Twenty-four hours after the last treatment, aortic rings were mounted in organ chambers for measurement of isometric force. Endothelium-dependent relaxations to acetylcholine and calcium ionophore were impaired by cyclosporin A but not affected by the vasodilators. Cyclosporin A-induced endothelial dysfunction was prevented by cotreatment with lisinopril or D 8731. Relaxations to nitroglycerin, SIN-1, and forskolin were not affected by any treatment. Contractions to phenylephrine and serotonin were reduced by lisinopril but not by D 8731. In contrast, contractions to angiotensin II were augmented by cyclosporin A, lisinopril, and the combination of both but not by D 8731 or D 8731 plus cyclosporin A. The data suggest a role for angiotensin II in cyclosporin A-induced endothelial dysfunction. Chronic ACE inhibition reduces overall smooth muscle contractility. The selective augmentation of angiotensin II effects by ACE inhibition and cyclosporin A suggests upregulation of angiotensin receptors in the aortic smooth muscle by these treatments. Chronic angiotensin subtype 1 receptor blockade does not appear to affect angiotensin receptor function.
Hypertension 1994 Jun
PMID:Vasomotor responses in cyclosporin A-treated rats after chronic angiotensin blockade. 820 13

The aim of this study was to determine whether angiotensin receptor subtypes play a role in angiotensin clearance from plasma. Angiotensin metabolic clearance rate was measured in rats by the constant infusion method. Increasing doses of angiotensin II were infused for 15 minutes, and blood was sampled for angiotensin II. The type 1 angiotensin II receptor antagonist losartan decreased the apparent metabolic clearance rate by > 50% at low-dose infusion, suggesting that type 1 angiotensin II receptors are involved in angiotensin II clearance from plasma. At higher angiotensin infusion rates, the-metabolic clearance rate of angiotensin was unaffected. To dissect the contribution of renin-generated angiotensin, additional experiments were performed in nephrectomized rats. In anephric rats, angiotensin clearance was unaffected by type 1 angiotensin II receptor inhibition. In contrast, the type 2 angiotensin II receptor ligand PD123319 in intact rats caused a > 50% increase in metabolic clearance rate of angiotensin at higher infusion rates (P < .05). In anephric rats, the type 2 angiotensin II receptor ligand alone or combined with type 1 receptor inhibition was without effect on the metabolic clearance rate or the T1/2 for angiotensin disappearance. These data argue against a role for type 1 or 2 angiotensin II receptors as clearance receptors. Increased clearance of angiotensin by type 2 receptor blockade in the presence but not the absence of kidneys suggests an alternative renal mechanism by which selective type 2 ligands may alter angiotensin effects.
Hypertension 1994 Jun
PMID:Effects of angiotensin receptor subtype inhibitors on plasma angiotensin clearance. 820 17

The roles of the sympathetic nervous system, angiotensin II, and arginine vasopressin in the cardiovascular-renal responses to nitric oxide synthesis inhibition were examined in eight conscious dogs equipped with arterial and venous catheters and a nonoccluding bladder catheter. Nitric oxide inhibition was achieved by intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME) at 37.1 nmol/kg per minute for 140 minutes in the control group. The same dogs, after a 1-week recovery, were pretreated for 2 days with either prazosin for alpha 1 blockade, prazosin plus propranolol for alpha 1 plus beta blockade, L-158,809 for angiotensin receptor blockade, or d(CH2)Tyr(Me)arginine vasopressin for vasopressin-V1 blockade, and the L-NAME infusion was repeated. After 140 minutes of L-NAME infusion into the control group, mean arterial pressure and renal vascular resistance had increased 16% and 71%, and renal blood flow, glomerular filtration rate, urine flow, and urinary sodium excretion had decreased 33%, 16%, 61%, and 64%, respectively. The decrement in renal blood flow and glomerular filtration during L-NAME administration was unaffected by any of the neurohumoral blockers. During V1 blockade L-NAME resulted in only a 3% increase in arterial pressure, attenuation of the renal vascular resistance response, and almost total elimination of the decrease in urine flow. During angiotensin blockade the L-NAME-induced increase in arterial pressure was markedly attenuated, and the decrease in urinary sodium excretion was attenuated in the alpha 1 plus beta blockade group.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jun
PMID:Mechanisms involved in the cardiovascular-renal actions of nitric oxide inhibition. 820 34

The effect of inhibiting the renin-angiotensin system was evaluated in male Sprague-Dawley rats with reduced renal mass produced by right nephrectomy and infarction of two-thirds of the left kidney. Separate groups of rats were then administered the angiotensin receptor antagonists, A-81988 or losartan (DuP 753), the angiotensin converting enzyme inhibitor, enalapril, or vehicle (tap water) in their drinking water for 4 weeks. Tail cuff blood pressures and blood samples were obtained weekly. Excretory function during week 4 was evaluated using metabolic cages. Rats with reduced renal mass were characterized by a significant elevation in systolic blood pressure and urinary protein excretion along with a reduced urine osmolality. At 1 mg/kg/day, A-81988 prevented the hypertension and the development of proteinuria. A-81988 administration also improved urinary concentrating ability because urine osmolality was significantly higher in this group compared to untreated controls. The same dose of losartan or enalapril was ineffective at controlling the development of the hypertension, indicating that A-81988 is more potent in vivo. Despite the maintenance of systemic hypertension, losartan significantly blunted the proteinuria compared to vehicle-treated controls. At a dose of 10 mg/kg/day, losartan and enalapril also prevented the increase in systolic blood pressure and proteinuria and produced an increase in urine osmolality. These data support the hypothesis that angiotensin receptor antagonists have beneficial effects in forms of renal failure associated with proteinuria and diminished concentrating ability.
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PMID:Angiotensin II receptor blockade improves renal function in rats with reduced renal mass. 824 38


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