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

Recent developments in the techniques of molecular biology and the availability of inhibitors of the renin-angiotensin system have provided new insight into renin-angiotensin research. The control mechanism of renin release and the metabolism of circulating renin have been well characterized on the molecular level. Angiotensin II has been shown to play an important role not only in the regulation of blood pressure but also in cell growth and hypertrophy. ACE inhibitors are effective for the treatments of hypertension and heart failure. Furthermore, recent studies suggest that ACE inhibitors may prevent atherosclerosis and glomerulosclerosis. Angiotensin II receptor antagonists have similar beneficial effects. These effects of ACE inhibitors and angiotensin II-receptor antagonists may be mediated by growth factors and the extracellular matrix.
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PMID:[Pharmacology of the renin-angiotensin system]. 795 18

Angiotensin II receptor binding sites in type 1 interstitial cells in the inner stripe of the outer medulla are readily labeled in vitro by the radioligand but not in vivo after systemic radioligand administration. In anesthetized rats, we investigated if reduced vascular delivery due to angiotensin II-induced renal vasoconstriction or, alternatively, prior occupancy of these sites by endogenous angiotensins modulates angiotensin II subtype 1 receptor binding to renal medullary interstitial cells in vivo using electron microscopic autoradiography. Using 125I-angiotensin II, administered systemically, as a radioligand, binding in control rats occurred predominantly in the glomeruli and proximal tubules, while only low binding was observed in the inner stripe of the outer medulla. Pretreatment of rats with unlabeled [Sar1,Ile8]angiotensin II or with the angiotensin II subtype 1 receptor antagonist losartan before receiving the radioligand completely abolished binding to all sites. Renal vasodilatation induced by sodium nitroprusside or use of the radiolabeled antagonist analogue 125I-[Sar1,Ile8]angiotensin II did not alter binding to the inner stripe. In contrast, chronic salt loading or inhibition of angiotensin-converting enzyme by perindopril significantly increased binding not only to the cortical sites but also to the sites in the inner stripe of the outer medulla. Electron microscopic autoradiographs of the inner stripe detected binding in the interstitial cells only in rats treated with chronic salt loading or perindopril. These results suggest that endogenous angiotensins may modulate binding of circulating angiotensin II to the interstitial cells in vivo, and these angiotensin II receptor-bearing cells are more likely to be more responsive to interstitial angiotensin II than to the circulating hormone.
Hypertension 1994 Jun
PMID:In vivo occupancy of angiotensin II subtype 1 receptors in rat renal medullary interstitial cells. 820 14

1. The combined effect of diabetes and hypertension on the plasma angiotensin II (AII)/glomerular AII receptor (AII-R) relationship in streptozotocin-induced diabetes was investigated as well as the effect of glycaemic control on this relationship. 2. Diabetes was induced in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with streptozotocin 60 mg/kg and blood sugars maintained between 18-21 mmol/L (uncontrolled diabetes) and 4-8 mmol/L (controlled diabetes). Rats were killed on days 1 and 7. Angiotensin II receptor was estimated by saturation analysis and plasma AII by radio-immunoassay. 3. Angiotensin II receptors were significantly higher in non-diabetic SHR than WKY rats (708 +/- 62 and 388 +/- 36 fmol/mg protein, respectively, P = 0.0008). Plasma AII were comparable in both groups (47 +/- 2.7, 38 +/- 3.5 pg/mL, respectively) and a significant inverse relationship between AII/AII-R was observed (WKY P = 0.02 and SHR P = 0.004). 4. On day 7, plasma AII and AII-R levels in diabetic groups were comparable with those of their non-diabetic controls. Diabetic WKY rats maintained an inverse correlation between AII and AII-R (controlled P = 0.04 and uncontrolled P = 0.015), but this did not occur in the SHR. 5. Absence of receptor response to varying ligand concentrations in the diabetic SHR may contribute to the development of nephropathy. Glycaemic control does not appear to reverse this abnormality in the SHR, so that co-existent hypertension may have a more direct influence on renal function.
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PMID:Abnormality of the glomerular angiotensin II receptor in experimental diabetic nephropathy. 832 23

Angiotensin II receptor antagonists represent a new class of drugs that provide a site-specific blockade of the effects of angiotensin II. Losartan potassium, the first compound of this drug class, has recently become available in the United States. The clinical experience with angiotensin II receptor antagonists has demonstrated that these drugs are safe and efficacious for the treatment of hypertension and, possibly, congestive heart failure. Unlike with angiotensin-converting enzyme inhibitors, the incidence of cough observed with angiotensin receptor antagonists is similar to that with placebo. Although several angiotensin receptors have been characterized, the effects of losartan and other angiotensin receptor antagonists under development are selective for the angiotensin II type 1 receptor. Unlike angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists do not inhibit bradykinin metabolism or enhance prostaglandin synthesis. The antihypertensive efficacy of the angiotensin receptor antagonists has been documented to be similar to that of angiotensin-converting enzyme inhibitors. If the findings of clinical studies corroborate the initial reports on efficacy and safety, it seems likely that the angiotensin receptor antagonists will be added to the list of drugs that have been deemed suitable for first-line therapy in the treatment of hypertension and congestive heart failure.
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PMID:Angiotensin II receptor inhibition. A new therapeutic principle. 882 49

The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure regulation and fluid and electrolyte homeostasis. Angiotensin converting enzyme inhibitors (ACEI) were the first of the RAAS blocking agents to be widely used in the treatment of hypertension and congestive heart failure. Angiotensin II receptor antagonists, another class of pharmacological blockers of the RAAS, have more recently been shown to be safe and useful in hypertension and perhaps also in heart failure. This review deals with the similarities and differences between these two classes of drugs with particular emphasis on the effects of the drugs on the heart, the blood vessels, the kidney (role of the drugs as nephroprotective), the brain, the hormonal profile and finally the potential adverse effects. The place of angiotensin II antagonists in congestive heart failure remains to be more precisely defined.
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PMID:[Comparison between the effects of angiotensin-converting enzyme inhibitors and angiotensin II antagonists]. 977 25

Angiotensin II receptor antagonists have become clinically available for the treatment of arterial hypertension. Presently, there is little information about their effects on BP, proteinuria, and renal function in patients with moderate or advanced renal failure. This study examines the effects of the angiotensin II antagonist Valsartan (80 mg/d) on proteinuria and glomerular permselectivity in patients with chronic renal failure during a 6-mo treatment, using a double-blind, randomized, placebo-controlled study (treatment group [V-group]: n = 5, age 57 +/- 7 yr, serum creatinine 365 +/- 122 micromol/L; placebo group [P-group]: n = 4, age 62 +/- 11 yr, serum creatinine 346 +/- 61 micromol/L). Study parameters included BP, 24-h proteinuria, GFR, and effective renal plasma flow (ERPF) as determined by inulin and para-aminohippurate clearance. Changes in glomerular permselectivity were assessed by measuring the fractional clearances of neutral dextrans by HPLC gel-permeation chromatography. Valsartan lowered the mean arterial pressure on average by 13 +/- 7 mmHg during the 6-mo treatment (P < 0.05). GFR and ERPF remained almost unchanged. However, after 6 mo of Valsartan treatment, proteinuria was reduced by 396 +/- 323 mg/24 h (26 +/- 18%) and albuminuria by 531 +/- 499 mg/24 h (41 +/- 21%) with regard to baseline values (P < 0.05). In the P-group, both proteinuria and albuminuria increased slightly with time (by 30 +/- 43% and 30 +/- 54%, respectively, NS). The fractional clearances of high molecular weight dextrans >66 A were significantly reduced after 6 mo of Valsartan treatment (P < 0.05), indicating a reduction of the glomerular shunt volume by 54 +/- 20% (P < 0.05) according to the model of Deen et al. (Am J Physiol 249: 347-389, 1985). The mean pore size radius of the glomerular membrane remained unchanged. This effect was independent of glomerular hemodynamic changes. Valsartan persistently lowered proteinuria in patients with chronic renal failure. Although GFR and ERPF remained nearly stable, this effect could be attributed to an improvement in glomerular permselectivity.
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PMID:Effects of the angiotensin II antagonist valsartan on blood pressure, proteinuria, and renal hemodynamics in patients with chronic renal failure and hypertension. 984 76

Pharmacological blockade of the renin-angiotensin system has been found to be a safe and efficacious way to treat hypertension and congestive heart failure. The success of the angiotensin converting enzyme inhibitors has led to interest in alternative ways to block the renin-angiotensin system. Angiotensin II receptor antagonists are a new class of anti-hypertensive drugs that provide a specific blockade of the effects of angiotensin II. Losartan potassium, the first compound of this class, has recently been approved in Japan. It seems likely that the angiotensin receptor antagonists will be suitable to first-line therapy and use of this class for treatment of hypertension will dramatically increase in Japan because of the excellent clinical and laboratory safety profiles.
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PMID:[Angiotensin II receptor antagonists: a review of the development and future perspective]. 1036 27

A disturbing pattern in the management of hypertension is emerging worldwide. More patients are being treated for hypertension, but blood pressures are not decreasing to target levels. Inadequate reduction in blood pressure is a risk factor for coronary artery disease. Poor drug efficacy, side effects, and lack of compliance are important factors leading to inadequate control of blood pressure. Angiotensin II receptor antagonists provide adequate 24-hour blood pressure control, as measured by ambulatory blood pressure monitoring, and have a side-effect profile similar to placebo. They also provide better patient compliance through once-daily dosing. This article compares the safety and efficacy of angiotensin II receptor antagonists with other antihypertensive agents.
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PMID:Safety and efficacy of angiotensin II receptor antagonists. 1043 39

Systolic hypertension is a major risk factor for cardiovascular disease. The determinants of systolic blood pressure are peripheral resistance and arterial compliance. Arterial vasoconstriction, vascular growth and fluid retention, induced by the renin-angiotensin system directly or indirectly by enhancing sympathetic nervous system activity, are important factors in increasing peripheral resistance, decreasing arterial compliance and, consequently, elevating systolic blood pressure. Selective blockade of the angiotensin II type 1 (AT1) receptor represents a novel mechanism for interrupting the renin-angiotensin system. This provides the additional benefit of blocking angiotensin II generated by non-angiotensin-converting-enzyme pathways without altering either bradykinin metabolism or the potential beneficial effects of AT2 receptor stimulation. Eprosartan is a potent (1.4 nmol/l) AT1 receptor antagonist that inhibits angiotensin-II-induced vascular contraction in a competitive manner. Eprosartan is effective in reducing disease progression in animal models of hypertension, heart failure, renal disease and stroke. Furthermore, eprosartan causes a large increase in arterial compliance in hypertensive rats fed high-salt and high-fat diets. Eprosartan also possesses sympathoinhibitory activity as demonstrated by an inhibition of the pressor responses induced by activation of sympathetic outflow through spinal cord stimulation in pithed rats. In contrast, other angiotensin II receptor antagonists, such as losartan, used at equivalent angiotensin II blocking activity, do not appear to alter sympathetic nervous system activity. Angiotensin II receptor antagonists, such as eprosartan, that have the ability to block both the direct effects of angiotensin II and the indirect effects mediated by enhanced sympathetic neurotransmission, may represent an important advance in the treatment of elevated systolic blood pressure.
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PMID:Pharmacological mechanism of angiotensin II receptor antagonists: implications for the treatment of elevated systolic blood pressure. 1046 64

The renin-angiotensin system has two roles in clinical hypertension: its vasoconstrictor properties directly govern blood pressure, and its actions on arterial smooth muscle, connective tissue, and endothelial integrity affect cardiovascular prognosis. Additionally, the direct actions of angiotensin II on the function and structure of the heart and renal vasculature influence clinical events. Angiotensin-converting enzyme (ACE) inhibitors have produced functional and clinical outcome benefits in clinical trials of patients with congestive heart failure, systolic dysfunction after myocardial infarction, and diabetic nephropathy. Similar favorable trends have been noted in observational studies in hypertension. Because such enzymes as chymase can substitute for ACE, the ACE inhibitors may not completely block angiotensin II formation, although they enhance bradykinin accumulation and secondarily stimulate nitric oxide and vasodilatory prostaglandins. Angiotensin II receptor blockers (ARB) selectively block the angiotensin II type 1 (AT1) receptor that not only mediates the known effects of angiotensin II but, according to recent reports, might be responsible for sequestering angiotensin II molecules in renal and cardiac cells. Moreover, by increasing plasma concentrations of angiotensin II, the ARB stimulate the unblocked angiotensin II type 2 (AT2) receptors, which-if they exist in meaningful numbers in human hypertension-mediate additional vasodilatory and antiproliferative effects. The contrasting actions of these two classes of drugs might be clinically relevant. For example, they may have additive antihypertensive efficacy; they have differing effects on renal plasma flow; and in a small pilot study of patients with congestive heart failure, the ARB demonstrated an apparent advantage in survival. Ongoing clinical trials will try to determine whether the effects of ARB can equal or even exceed the beneficial effects of ACE inhibitors on cardiovascular prognosis.
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PMID:Interrupting the renin-angiotensin system: the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of hypertension. 1061 71


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