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

This study was designed to assess the contribution of thromboxane (Tx) A2 to the pathogenesis of renal dysfunction in rats with angiotensin II (Ang II)-salt hypertension. Hypertension was induced in rats drinking 0.15 mol/l NaCl by infusion of Ang II (125 ng/min, intraperitoneally) for 12 days. Relative to values in water- and saline-drinking rats without Ang II infusion, rats with Ang II-salt hypertension exhibited increased renal vascular resistance, decreased renal blood flow, and increased renal excretion and glomerular synthesis of TxB2. Treatment with an inhibitor of TxA2 synthesis, UK 38,485, had no effect on renal function in normotensive and hypertensive rats. Similarly, the TxA2 and prostaglandin endoperoxide antagonist SQ 29,548 did not affect renal function in normotensive rats. In contrast, in rats with Ang II-salt hypertension of 12 days' duration, SQ 29,548 caused a reduction in renal vascular resistance, allowing for maintenance of renal blood flow in the face of an accompanying reduction in blood pressure. A comparable reduction in renal perfusion pressure, produced by constriction of the abdominal aorta above the renal arteries, was not accompanied by a reduction in renal vascular resistance in Ang II-salt hypertensive rats. Therefore, the SQ 29,548-induced lowering of renal vascular resistance is attributable not to renal blood flow autoregulation, but to blockade of the renal vasoconstrictor actions of TxA2 and/or prostaglandin endoperoxides. This interpretation implies that pressor eicosanoids contribute to increase renal vascular resistance in rats with severe Ang II-salt hypertension.
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PMID:Renal function in rats with angiotensin II-salt-induced hypertension: effect of thromboxane synthesis inhibition and receptor blockade. 215 60

Stimulation of proximal tubular fluid reabsorption by peritubular angiotensin II (Ang II) was examined by split-drop micropuncture in 5- and 12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY). In WKY, the maximum stimulation occurred at 10(-11) mol/l and the response did not vary with age. In 5-week-old SHR, the dose-response relationship was similar in shape and in the extent of the maximum response but was shifted one half-logarithmic step to the right, indicating decreased sensitivity to Ang II. In contrast, the dose-response relationship was shifted one half-logarithmic step to the left in 12-week-old SHR compared with WKY. Alterations in the responsiveness of the proximal tubule to Ang II in young SHR could contribute to sodium retention observed during development of hypertension in these rats.
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PMID:Altered responsiveness of proximal tubule fluid reabsorption of peritubular angiotensin II in spontaneously hypertensive rats. 216 13

Diabetes-associated hypertension is accompanied by high levels of body sodium and cardiovascular hyper-reactivity to noradrenaline. Captopril, a promising drug for the treatment of hypertension in diabetics, may influence sodium metabolism and adrenergic pathways. This possibility was investigated in 11 patients with non-azotaemic diabetes mellitus and hypertension, studied after a 3-week placebo phase and after an 8-week phase of captopril treatment (50-100 mg/day). Blood pressure, exchangeable body sodium, blood volume, plasma renin activity, angiotensin II (Ang II), aldosterone, catecholamine levels and the pressor reactivity to infused Ang II or noradrenaline were measured. Compared with placebo, captopril caused a significant decrease in arterial pressure and stimulation of plasma renin activity. Exchangeable sodium, blood volume, plasma Ang II, aldosterone, noradrenaline and adrenaline levels, the pressor and aldosterone responsiveness to infused Ang II and the pressor response to infused noradrenaline (alone or combined with atropine) were not modified. These findings suggest that in hypertensive diabetics angiotensin converting enzyme inhibition causes a marked decrease in blood pressure. The mechanism of action is unrelated to changes in body sodium or noradrenergic-dependent pressor reactivity. In the stable phase of therapy, Ang II-dependent pathways are left unaltered when captopril is administered twice a day.
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PMID:Cardiovascular regulation during angiotensin converting enzyme inhibition with captopril in diabetes-associated hypertension. 216 58

Spontaneously hypertensive Okamoto-strain rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were actively immunized with mouse renin to investigate the effect on blood pressure of blocking the renin-angiotensinogen reaction. Ten male SHR and 10 male WKY rats were immunized with purified mouse submandibular gland renin. Control rats were immunized with bovine serum albumin. Antirenin antibodies were produced by both SHR and WKY rats, but renin-immunized SHR had higher titers of circulating renin antibodies after three injections. The increase in renin antibody in renin-immunized SHR was associated with a significant drop in blood pressure (tail-cuff method) that became similar to that of the WKY control rats after four injections. The blockade by antirenin immunoglobulins of the renin-angiotensinogen reaction also decreased the blood pressure of normotensive rats. Perfusion of renin-immunized rats with mouse submandibular renin (10 micrograms) in vivo caused no increase in blood pressure. Perfusion of renin-immunized, salt-depleted SHR with converting enzyme inhibitor caused no further decrease in blood pressure but significantly decreased blood pressure in salt-depleted control rats. The presence of circulating renin antibodies was associated with low plasma renin activity (0.31 +/- 0.23 ng angiotensin I [Ang I]/ml/hr). Plasma renin activity was unchanged in control animals (13.1 +/- 3.9 ng Ang I/ml/hr in control SHR, 13.9 +/- 3.2 ng Ang I/ml/hr in control WKY rats). Renin antibody-rich serum produced a dose-dependent inhibition of rat renin enzymatic activity in vitro. The chronic blockade of the renin-angiotensinogen reaction in renin-immunized SHR produced an almost-complete disappearance of Ang II (0.8 %/- 7 fmol/ml; control SHR, 30.6 +/- 15.7 fmol/ml) and a 50% reduction in urinary aldosterone. Renin immunization was never associated with a detectable loss of sodium after either 10 or 24 weeks. The glomerular filtration rate was not decreased 10 weeks after renin immunization, whereas blood pressure was significantly decreased, plasma renin activity was blocked, and renal plasma flow was increased. The ratio of left ventricular weight to body weight after 24 weeks was significantly below control levels in renin-immunized WKY rats and SHR. Histological examination of the kidney of renin-immunized SHR showed a chronic autoimmune interstitial nephritis characterized by the presence of immunoglobulins, mononuclear cell infiltration, and fibrosis around the juxtaglomerular apparatus. These experiments demonstrate that chronic specific blockade of renin decreases blood pressure in a genetic model of hypertension in which the renin-angiotensin system is not directly involved.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Physiological and immunopathological consequences of active immunization of spontaneously hypertensive and normotensive rats against murine renin. 218 56

The Ca2+, calmodulin (CaM)-dependent phosphorylation of the 20 kDa myosin light chain (LC20) is accepted as an important component of the regulatory mechanism in smooth muscle contraction. Since we have originally developed selective inhibitors of each process of the intracellular Ca2+ messenger system, the effect of a newly synthesized compound ML-9, a myosin light chain kinase (MLCK) inhibitor on superprecipitation of actomyosin, isometric tension development and phosphorylation of LC20 in vascular smooth muscle was investigated. Superprecipitation of actomyosin from bovine aorta was inhibited by the addition of ML-9 in a dose-dependent manner. In chemically skinned smooth muscle cells of the rabbit mesenteric artery, ML-9 inhibited both Ca2+ and Ca2+, CaM-independent MLCK-induced contraction. In the intact vascular strips, increase in LC20 phosphorylation reached a maximal value within 10 sec from a resting value, and then declined to near the basal level during the maintained isometric force developed in response to 50 mmol/L KCl. Both the maximal rate and extent of KCl-induced contraction and the phosphorylation of LC20 were also inhibited by ML-9. It antagonized the contraction induced by various contractile agonists, such as NE, 5HT, His, and Ang II concomitant with the inhibition of LC20 phosphorylation. These results suggest that ML-9 inhibits the actin-myosin interaction through the modulation of LC20 phosphorylation via the inhibition of MLCK activity. ML-9 will aid in determining pathophysiological functions of MLCK of increased vascular contractility in hypertension.
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PMID:Molecular pharmacology of calcium, calmodulin-dependent myosin phosphorylation in vascular smooth muscle. 222 74

The effect of microinjection into the nucleus tractus solitarii (NTS) of angiotensin II (Ang II) on baroreceptor control of heart rate (HR) in conscious, freely moving rats was evaluated with a new method of long-term cannulation of the dorsal brainstem areas. Reflex changes in HR were produced by intravenous bolus injections of either phenylephrine or sodium nitroprusside (0.2-25.6 micrograms/kg) both after saline and after unilateral microinjection of Ang II into the NTS (24 ng, 0.2 microliter) and compared with those produced after administration of Ang II into the fourth ventricle (24 ng, 0.2 microliter) or intravenously (1-2 ng/kg/min). Baseline levels of mean arterial pressure (MAP) and HR were not affected by the route of Ang II application but reflex bradycardia during MAP increase was significantly attenuated after injections of Ang II into the NTS. Both the slope and the intercept of the regression line function between delta HR and delta MAP were reduced by 43% from the control value of -1.55 +/- 0.13 beats/min/mm Hg (p less than 0.01) and -14 +/- 5 beats/min (p less than 0.05), respectively. Similar reductions were observed after Ang II administration into the fourth ventricle or intravenously, although microinjections into the cerebellum produced no effect. Endogenous blockade of Ang II by saralasin (22 ng) in the NTS facilitated the bradycardic response (-2.29 +/- 0.91 beats/min/mm Hg). Nitroprusside-induced tachycardia was not altered by Saralasin microinjection into the NTS or by Ang II application to the NTS, fourth ventricle, or intravenously.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Feb
PMID:Angiotensin II as a modulator of baroreceptor reflexes in the brainstem of conscious rats. 229 76

To assess the rate of activation of the renin-angiotensin-aldosterone axis and enhancement of adrenal responsiveness to angiotensin II (Ang II) with restriction of sodium intake, 16 healthy male subjects were placed initially on a 200 meq daily sodium intake; adrenal responsiveness to Ang II was assessed, and then daily sodium intake was reduced abruptly to 10 meq. Adrenal responses to Ang II were assessed again during the non-steady state interval 24 and 48 hours later, and after balance was achieved in 5-7 days. Renin-angiotensin system activation was evident within 24 hours after sodium intake was restricted. The increase in basal plasma aldosterone concentration and enhancement of the adrenal response to Ang II, on the other hand, tended to lag. Within 24 hours of restricting sodium intake, despite a significant increase in both plasma renin activity (1.0 +/- 0.2 vs. 2.4 +/- 0.7 ng/ml/hr, p less than 0.01) and Ang II concentration (22.0 +/- 1.9 vs. 29.5 +/- 1.3 pg/ml, p less than 0.05), there was no increase in basal plasma aldosterone concentration (10.4 +/- 1.3 vs. 11.7 +/- 1.2 ng/dl). At 48 hours, despite little further change in plasma renin activity or plasma Ang II concentration, there was a sharp increase in basal plasma aldosterone concentration (22.5 +/- 3.6 ng/dl, p less than 0.01). The adrenal response to Ang II was increased significantly at 24 hours, evident at only a 10 ng/kg/min dose, but showed progressive further enhancement with time.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Apr
PMID:Time course of enhanced adrenal responsiveness to angiotensin on a low salt diet. 231 19

The present study was designed to study the functional properties of Angiotensin II (Ang II) binding sites in vascular smooth muscle cells in the Milan hypertensive rat (MHS), a model of low renin hypertension. Smooth muscle cells from MHS rats exhibited increased growth in culture in comparison with the Milan normotensive strain (MNS) as determined by population doubling times (24.5 +/- 2 and 34.8 +/- 2 hours, n = 4, respectively). Hormone receptor number, evaluated by binding assays using [125I]Ang II, showed no difference in either receptor number or affinity for both cell types. The functional responsiveness of Ang II receptors was evaluated by measuring the activation of phospholipase C, Na(+)-H+ exchange, and cytosolic Ca2+ levels. Phospholipase C activity was determined as tritium-labeled inositol trisphosphate and bisphosphate release before and after 15-second exposure to 10(-7) M Ang II. Ang II-stimulated phospholipase C activity in MNS (p less than 0.02) but not in MHS cells. Na(+)-H+ exchange was measured as the dimethylamiloride-sensitive 22Na+ influx into acid-loaded vascular smooth muscle cells with and without 10(-7) M Ang II. In MNS cells, Ang II significantly stimulated (p less than 0.001) antiporter activity but not in MHS cells, which showed a uniformly blunted response. MHS cells exhibited higher basal cytosolic Ca2+ levels than MNS cells, but Ca2+ rapidly increased in the presence of Ang II in MNS but not in MHS cells. Direct activation of phospholipase C by GTP-gamma-S in permeabilized cells indicated that both strains exhibited similar coupling levels by guanine-nucleotide binding proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Jun
PMID:Vascular smooth muscle cells from the Milan hypertensive rat exhibit decreased functional angiotensin II receptors. 234 21

A series of nonpeptide angiotensin II (Ang II) receptor antagonists was evaluated in rat adrenal cortical microsomes for their inhibitory effects on the specific binding of [3H]Ang II, in the isolated rabbit aorta bioassay for their functional antagonism of contractile response to Ang II, and in high renin, renal-hypertensive rats for their intravenous antihypertensive effects, expressed as IC50, pA2, and intravenous ED30, respectively. Highly significant linear correlations were found between IC50 and pA2 (r = -0.88), between IC50 and intravenous ED30 (r = 0.79), and between pA2 and intravenous ED30 (r = -0.93). In both in vitro and in vivo functional assays, none of these antagonists exhibited agonistic effects. The orally active nonpeptide Ang II receptor antagonists EXP9270 and DuP 753 (oral ED30 = 3.6 and 0.59 mg/kg, respectively) were selected for further characterization. These antagonists exhibited selective and competitive Ang II antagonism in rabbit aorta and guinea pig ileum. In conscious normotensive rats, DuP 753 abolished the pressor response to saralasin, suggesting that the pressor effect of saralasin is attributed to its Ang II-like activity. In addition, DuP 753 also blocked the Ang II-induced drinking response and aldosterone release in rats. These results suggest that Ang II receptor blockade is the primary mechanism of the antihypertensive effect of these nonpeptide Ang II receptor antagonists. Further, the specificity and lack of partial agonistic effects of these molecules make them potentially useful physiological probes and therapeutic agents.
Hypertension 1990 Jun
PMID:Nonpeptide angiotensin II receptor antagonists. Studies with EXP9270 and DuP 753. 235 36

New findings from this laboratory suggest that fragments of angiotensin derived from the amino (N-)terminus are biologically active end products of the renin-angiotensin system. In vitro and in vivo experiments revealed that the heptapeptide angiotensin-(1-7) [Ang-(1-7)] is a major endogenous product of the renin-angiotensin system cascade in the brains of rats and dogs. Additional studies with enzyme inhibitors showed that Ang-(1-7) is produced directly from angiotensin I by an enzyme other than the angiotensin converting enzyme. Immunocytochemical fibers within the hypothalamo-neurohypophyseal vasopressinergic system of the rat. Although Ang-(1-7) is as potent as angiotensin II (Ang II) in stimulating release of vasopressin from superperfused hypothalamo-neurohypophyseal explants, the heptapeptide has no dipsogenic or vasoconstrictor activity. In contrast, Ang-(1-7) mimics the effects of Ang II in augmenting the intrinsic discharge rate of neurons within the vagal-solitary complex and in causing monophasic depressor responses after microinjection into the medial region of the nucleus tractus solitarii. The evidence obtained in these experiments suggests novel mechanisms for the generation of angiotensin peptides in the brain. Additionally, the findings suggest that some of the biological actions ascribed to Ang II might be conveyed by the endogenous production of other angiotensin peptides that are generated by enzymatic pathways alternate to those described in the peripheral circulation.
Hypertension 1990 Feb
PMID:Pathways of angiotensin formation and function in the brain. 240 55


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