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

1. The metabolic role of arterial angiotensin I-forming enzyme (i.e. renin activity) was studied in total homogenates and in subcellular fractions of the aorta of normotensive and hypertensive rats. 2. Angiotensin I-forming enzyme was measured in (a) uninephrectomized rats rendered hypertensive with D-aldosterone and sodium chloride (10 g/l drinking solution, (b) rats treated in the same manner but with the addition of spironolactone, and (c) control rats. 3. Hypertension developed in aldosterone-treated rats within 3-6 weeks and was associated with decreased plasma and renal renin values. Total aortic renin activity was up to sixfold higher in the hypertensive animals than in control animals and there was an increased ratio of supernatant to microsomal renin activity in the aorta. 4. In spironolactone-treated rats blood pressure and total aortic renin concentrations were comparable with those in the control rats. 5. The results support the hypothesis that renin generated at local vascular sites, which is independent of circulating renin levels, contributes to regulation of blood pressure.
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PMID:Effects of aldosterone and spironolactone on arterial renin in rats. 107 85

The examinations were carried out for 93 selected women divided into premenopausal group and the group in the early stage of postmenopausal period. Each of these groups was subdivided into two subgroups with normal blood pressure and arterial hypertension. The catecholamine level were determined fluorimetrically as per Euler and Lishajko, and the level of dopamine in plasma using Nagatsu's method. Angiotensin I and aldosterone concentration in serum was determined by radioimmunoassay using RIA set of Sorin. Free catecholamine excretion with urine for women with arterial hypertension in the premenopausal period is highly statistically (p < 0.001), and in the postmenopausal period only epinephrine is statistically higher (p < 0.01), whereas the dopamine level in plasma is smaller, statistically significant only in premenopausal period (p < 0.05). Also for women with the arterial hypertension compared with the control group the angiotensin I and aldosterone concentration in serum is statistically smaller.
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PMID:[Levels of catecholamines and activity of the renin-aldosterone system in women with hypertension in the period before and after menopause]. 130 31

We examined the angiotensin-induced potentiation of noradrenergic transmission in the isolated mesenteric arteries of one-kidney, one clip (1K1C) hypertensive rats. The angiotensin converting enzyme activity measured in plasma did not change during the development of hypertension, whereas the activity measured in the aortic tissue was significantly augmented 28 days after the renal artery was clipped. Although the pressor responses to nerve stimulation were basically unaltered, a significant increase in the sensitivity to norepinephrine developed during hypertension. The 1K1C preparations presented an increased sensitivity to the facilitatory effect of angiotensin II on the response to periarterial nerve stimulation. The facilitatory effect of angiotensin II on both nerve stimulation and exogenous norepinephrine was blocked by saralasin. Angiotensin I induced similar facilitatory action on noradrenergic transmission that was inhibited by saralasin. When a high concentration of angiotensin I was used, the facilitatory effect was significantly higher in mesenteric arteries from 1K1C rats than in controls. Captopril reduced the facilitatory effect of angiotensin I in 1K1C preparations, whereas the responses of the normotensive control rats were unaffected by captopril. These findings are consistent with angiotensin I acting directly on angiotensin II receptors or with angiotensin I being converted to angiotensin II by an alternative pathway not involving angiotensin converting enzyme.
Hypertension 1992 Feb
PMID:Facilitation of noradrenergic transmission by angiotensin in hypertensive rats. 131 Apr 83

We investigated the processing enzymes involved in the formation of circulating angiotensin-(1-7) after intravenous administration of angiotensin I to conscious spontaneously hypertensive and Wistar-Kyoto rats. Immunoreactive products, including angiotensin I, angiotensin II, and angiotensin-(1-7), were measured in arterial blood by three specific radioimmunoassays. Angiotensin I infusion (2 nmol) induced a rapid increase in immunoreactive angiotensin II and angiotensin-(1-7). Pretreatment with the angiotensin converting enzyme inhibitor enalaprilat (2 mg/kg) eliminated angiotensin II formation and augmented circulating levels of angiotensin I and angiotensin-(1-7) in spontaneously hypertensive and Wistar-Kyoto rats. The elevated levels of angiotensin-(1-7) in enalaprilat-treated rats were blocked by concurrent treatment with the neutral endopeptidase (EC 3.4.24.11) inhibitor SCH 39,370 (15 mg/kg) in both strains. Administration of SCH 39,370 alone decreased angiotensin-(1-7) levels in spontaneously hypertensive rats, whereas angiotensin II levels increased in both strains (p less than 0.01). Comparisons of the metabolism of angiotensin I in the two rat strains showed increased formation of angiotensin-(1-7) in spontaneously hypertensive rats not given any of the enzyme inhibitors. In addition, levels of angiotensin I were higher after administration of SCH 39,370 in hypertensive rats. These novel findings reveal that neutral endopeptidase EC 3.4.24.11 participates in the conversion of angiotensin I to angiotensin-(1-7) and in the metabolism of angiotensin II in the circulation of both spontaneously hypertensive and Wistar-Kyoto rats. Our results suggest that neutral endopeptidase EC 3.4.24.11 is a major enzymatic constituent of the circulating renin-angiotensin system.
Hypertension 1992 Jun
PMID:In vivo metabolism of angiotensin I by neutral endopeptidase (EC 3.4.24.11) in spontaneously hypertensive rats. 131 52

The demonstration of all components of the renin-angiotensin system in vascular tissue has raised questions as to the precise location of the local angiotensin II generation within the vascular wall. We investigated the metabolism of angiotensin I to angiotensin II in the vascular wall in the isolated rabbit thoracic aorta. Angiotensin I (3 x 10(-9) M) applied into the aortic lumen was partially converted to angiotensin II (14% after 60 minutes), but most of the luminal angiotensin I was degraded to peptide fragments or diffused as intact angiotensin I, peptide fragments, or both, into the vessel wall. Incubation studies with [3H]angiotensin I revealed that angiotensin I or angiotensin I fragments mainly diffused into the medial layer of the aorta and to a lesser degree into the adventitia and the endothelium. After removal of the endothelium, angiotensin II generation could no longer be detected. Addition of the angiotensin converting enzyme inhibitor ramiprilat (10(-7) M) to the incubation medium led to a complete blockade of angiotensin II generation by endothelial angiotensin converting enzyme. Our results underline the importance of the endothelium for conversion of angiotensin I to angiotensin II and provide evidence that conversion of angiotensin I to angiotensin II is predominantly achieved by endothelial cells. They also support the concept of an endocrine versus autocrine/paracrine renin-angiotensin system where the endothelium of the vasculature is the critical target site for angiotensin II production by both systems and, thus, the most important site for the actions of angiotensin converting enzyme inhibitors.
Hypertension 1992 Aug
PMID:Distribution and metabolism of angiotensin I and II in the blood vessel wall. 163 56

Angiotensin II stimulates prostaglandin release in blood vessels via activation of angiotensin receptors present in endothelium, vascular smooth muscle cells, or both. We evaluated the response of angiotensin II, angiotensin I, and [des-Phe8] angiotensin II [angiotensin-(1-7)] on prostaglandin release in porcine aortic endothelial cells. Incubation of cell monolayers with angiotensin I and angiotensin-(1-7), but not angiotensin II, stimulated the release of prostaglandin E2 and prostaglandin I2 in a dose-dependent manner (10(-10) to 10(-6) M) with an EC50 of approximately 1 nM. In addition, we characterized the angiotensin receptor subtypes mediating prostaglandin synthesis by using subtype-selective antagonists. Angiotensin I-stimulated prostaglandin synthesis was not altered by either of the nonselective classical angiotensin receptor antagonists [Sar1,Thr8]angiotensin II or [Sar1,Ile8]angiotensin II. In contrast, either the angiotensin subtype 1 (AT1) antagonist DuP 753 or the subtype 2 (AT2) antagonist CGP42112A significantly attenuated the prostaglandin release in response to angiotensin I. However, PD123177, another AT2 antagonist, did not inhibit angiotensin I-stimulated prostaglandin release. Angiotensin-(1-7)-induced prostaglandin release was significantly attenuated by [Sar1,Thr8]angiotensin II (10(-6) M) and PD123177 (10(-6) M) but not by [Sar1,Ile8]angiotensin II, DuP 753, or CGP42112A. Higher doses (10(-5) M) of DuP 753 and CGP42112A attenuated the angiotensin-(1-7) response. These data suggest that in porcine aortic endothelial cells, angiotensin I and angiotensin-(1-7) but not angiotensin II are potent stimuli for prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Stimulation of endothelial cell prostaglandin production by angiotensin peptides. Characterization of receptors. 173 95

To examine and characterize the vascular renin--angiotensin system in low-renin models of renal hypertension with and without the presence of overt renal insufficiency, we studied the formation and metabolism of angiotensin in isolated perfused rat hindquarter preparations. Rats with 5/6 nephrectomy (5/6NX) and rats with one-kidney, one clip (1K1C) hypertension were compared to sham operated (sham) animals. Angiotensin peptides in plasma or perfusate were characterized by high-performance liquid chromatography and radioimmunoassay (RIA). Plasma angiotensin II was lower, and blood pressure was higher in both experimental groups, compared to sham animals. Plasma angiotensinogen, measured by both direct and indirect RIA, was increased in both experimental groups. The spontaneous release of angiotensin I and angiotensin II from perfused hindquarters did not differ between the groups. Angiotensin I conversion was not different in 5/6NX or 1K1C groups compared with controls. Furthermore, angiotensin conversion was completely inhibited by captopril (1 mumol/l) in all groups. Renin-induced angiotensin release was significantly increased in 5/6NX as compared with sham rats, whereas there was no difference in renin-induced angiotensin release between 1K1C and sham animals. Angiotensin II degradation was significantly attenuated in 5/6NX rats when compared with sham rats (27.6% versus 53.9%, respectively, P less than 0.05) but was unaltered in 1K1C rats. Thus, in chronic uremic hypertension, renin-induced angiotensin formation was increased in the face of decreased angiotensin II degradation. These data suggest that vascular angiotensin may contribute to the elevated blood pressure observed in chronic renal failure. In 1K1C rats, vascular angiotensin formation and metabolism was unchanged despite suppressed plasma angiotensin II.
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PMID:Local angiotensin formation in hindlimbs of uremic hypertensive and renovascular hypertensive rats. 184 58

To study the metabolism and production of angiotensin I, highly purified monoiodinated [125I] angiotensin I was given by constant systemic intravenous infusion, either alone (n = 7) or combined with unlabeled angiotensin I (n = 5), to subjects with essential hypertension who were treated with the angiotensin converting enzyme inhibitor captopril (50 mg b.i.d.). Blood samples were taken from the aorta and the renal, antecubital, femoral, and hepatic veins. [125I]Angiotensin I and angiotensin I were extracted from plasma, separated by high-performance liquid chromatography, and quantitated by gamma counting and radioimmunoassay. Plasma renin activity was measured at pH 7.4. The plasma decay curves after discontinuation of the infusions of [125I]angiotensin I and unlabeled angiotensin I were similar for the two peptides. The regional extraction ratio of [125I]angiotensin I was 47 +/- 4% (mean +/- SEM) across the forearm, 59 +/- 3% across the leg, 81 +/- 1% across the kidneys, and 96 +/- 1% across the hepatomesenteric vascular bed. These results were not different from those obtained for infused unlabeled angiotensin I. Despite the rapid removal of arterially delivered angiotensin I, no difference was found between the venous and arterial levels of endogenous angiotensin I across the various vascular beds, with the exception of the liver where angiotensin I in the vein was 50% lower than in the aorta. Thus, 50-90% of endogenous angiotensin I in the veins appeared to be derived from regional de novo production. The blood transit time is 0.1-0.2 minute in the limbs and in the kidneys and 0.3-0.5 minute in the hepatomesenteric vascular bed. This is too short for plasma renin activity to account for the measured de novo angiotensin I production. It was calculated that less than 20-30% in the limbs and in the kidneys and approximately 60% in the hepatomesenteric region of de novo-produced angiotensin I could be accounted for by circulating renin. These results indicate that a high percentage of plasma angiotensin I may be produced locally (i.e., not in circulating plasma).
Hypertension 1990 Jan
PMID:Metabolism and production of angiotensin I in different vascular beds in subjects with hypertension. 240 79

Experiments were conducted to compare the relative importance of the local renin-angiotensin systems in the rabbit renal and femoral vascular beds and their functional role in hemodynamic regulation. Angiotensin I (Ang I) (0.15 microgram/kg i.v.) elevated mean arterial blood pressure by 18 +/- 1 mm Hg in the renal experimental group and 19 +/- 1 mm Hg in the femoral experimental group; it decreased renal blood flow by 35 +/- 3% but increased femoral blood flow by 31 +/- 8%. All these effects were blocked by intravenous administration of captopril (2 mg/kg bolus injection plus 1 mg/kg/hr). Captopril also lowered mean arterial pressure by 17 +/- 3 and 16 +/- 2 mm Hg in the renal and femoral experimental groups, respectively, and it increased renal blood flow by 32 +/- 10% but reduced femoral blood flow by 21 +/- 4%. As a result, renal vascular resistance was decreased by 36 +/- 5%, but femoral vascular resistance remained unchanged. After captopril, plasma angiotensin II (Ang II) levels were decreased and Ang I levels increased in the two groups. The renal venous-arterial difference of Ang I was increased by captopril, but the femoral venous-arterial difference of Ang I was not, suggesting greater generation of Ang I in the kidney. In a separate group of bilateral nephrectomized rabbits, plasma Ang II levels as well as mean arterial pressure, femoral blood flow, and femoral vascular resistance were not changed by intravenous administration of captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Feb
PMID:In vivo comparison of renal and femoral vascular sensitivity and local angiotensin generation. 240 98

Experiments were designed to elucidate the effects of S-nitrosocaptopril (SnoCap) on vascular reactivity. Rings of bovine femoral and coronary arteries were mounted for isometric tension recording in physiological saline solution. SnoCap induced dose-dependent relaxations in both the coronary and femoral arteries, but inhibited contractions in the coronary artery to a significantly greater degree. Relaxations to SnoCap were inhibited by methylene blue. Angiotensin I and angiotensin II induced dose-dependent contractions in the bovine femoral artery. The angiotensin II antagonist saralasin induced comparable inhibition of the response to angiotensin I and angiotensin II. Captopril (10(-6) M) and SnoCap (10(-6) M) equally inhibited contraction to angiotensin I, inducing a 50-fold shift in the dose-response curve. SnoCap inhibited contraction to angiotensin II, inducing a 5-fold shift in the dose-response curve and depressing the maximum response. In summary, the S-nitrosylated derivative of captopril is a unique compound that inhibits vascular reactivity through activation of soluble guanylate cyclase and inhibition of angiotensin converting enzyme. This combined nitrovasodilator and angiotensin converting enzyme inhibitor may have clinical utility in hypertension, coronary artery disease and congestive heart failure.
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PMID:S-nitrosocaptopril. II. Effects on vascular reactivity. 265 77


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