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

We used the calcium-sensitive fluorescent indicator quin 2 to monitor changes in cytosolic free calcium concentration ([Ca2+]i) associated with angiotensin II receptor activation in cultured vascular smooth muscle cells isolated from rat aorta. Resting [Ca2+]i in unstimulated vascular smooth muscle cells was 198 +/- 7 nM. Angiotensin II induced concentration-dependent rapid increases in [Ca2+]i (threshold congruent to 10(-11) M; effective concentration, 50% congruent to 5 X 10(-10) M; maximum congruent to 10(-8) M); the rate of increase in [Ca2+]i also appeared to be concentration dependent. The angiotensin II-induced changes were completely blocked by the angiotensin II receptor antagonist [Sar1, Ile8]-angiotensin II. In the presence of extracellular calcium, 10(-8) M angiotensin II induced an increase in [Ca2+]i that reached peak values of five to six times the resting levels within 15 seconds, followed by a gradual decline to a plateau at two to three times the resting level. When EGTA was added to chelate external calcium, the angiotensin II-induced increases in peak [Ca2+]i were attenuated and the plateau phase was abolished. These data show that (1) quin 2 can be used in cultured vascular smooth muscle cells to study changes in calcium homeostasis induced by angiotensin II, and (2) angiotensin II acts on cultured vascular smooth muscle cells to cause a rapid increase in [Ca2+]i that appears to depend on both the mobilization of intracellular calcium and the influx of extracellular calcium.
Hypertension
PMID:Angiotensin increases cytosolic free calcium in cultured vascular smooth muscle cells. 392 84

Although potassium is known to lower blood pressure in a number of forms of experimental and human hypertension, the mechanism for this effect remains unclear. We studied several possible mechanisms for this effect in the spontaneously hypertensive rat (SHR). Fourteen-week-old SHR were given 0.5% KCl in the drinking water. This potassium supplement resulted in a 16-mmHg fall in mean arterial pressure and a 22% decrease in peripheral vascular resistance. Plasma potassium increased 0.4 meq/l, while muscle potassium was unchanged. Potassium supplementation resulted in no change in plasma renin activity, plasma aldosterone, or plasma norepinephrine. Urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha was also not altered by potassium supplementation. Potassium-supplemented SHR were found to have no difference in sodium excretion compared with control SHR, and plasma volume was similar in both groups. The pressor response to angiotensin II and norepinephrine was not substantially affected by potassium supplementation. Furthermore, baroreflex control of heart rate was not altered by potassium supplementation. Finally, potassium supplementation resulted in no change in mesenteric artery angiotensin II receptor number or receptor affinity. Therefore, although potassium lowers blood pressure in the SHR by decreasing peripheral vascular resistance, the mechanism of this effect on vascular resistance remains unknown.
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PMID:Cardiovascular and endocrine effects of potassium in spontaneously hypertensive rats. 406 67

To clarify a role of brain angiotensin II receptor binding in development of hypertension, the regional distribution and extent of specific angiotensin II binding were studied in salt-loaded normotensive (NTR) and spontaneously hypertensive (SHR) rats, and Goldblatt one-kidney hypertensive rat (GB). Further, angiotensin-converting enzyme activity was measured in these rats' brains. In control rats, angiotensin Ii receptor binding was consistently lower in the thalamus, hypothalamus, midbrain, striatum and cortex of SHR rats than in NTR rats. In GB rats, the binding capacity in the thalamus was greater than that of NTR rats. Sodium intake resulted in a rise in the receptor binding capacity in the hypothalamus, thalamus and striatum of SHR rat, whereas it did in a fall in the binding capacity in the hypothalamus, thalamus, striatum, midbrain and cortex of NTR rats. Angiotensin-converting enzyme activity was significantly elevated in the midbrain of salt-loaded SHR rats.
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PMID:A possible role of the brain angiotensin II receptor binding in development of hypertension. 627 98

Potassium depletion causes hypotension in normotensive animals and can lower the blood pressure in hypertensive animals and humans. Potential mechanisms for this hypotensive effect include a decrease in aldosterone levels, a decrease in vasopressin, and decreased responsiveness to the pressor effects of angiotensin II. The decreased response to angiotensin II could result from increased prostaglandin production, receptor occupancy, or a decrease in angiotensin II receptor affinity. A high potassium intake has no effect on blood pressure in normotensive animals and humans, but lowers blood pressure in those with hypertension. Mechanisms for this antihypertensive effect include natriuresis with sodium depletion, a decrease in plasma renin activity, an alteration in the neurogenic components of blood pressure regulation, and effects on resistance vessels related either to a high potassium concentration or to a decrease in the number of angiotensin II receptors.
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PMID:Effects of potassium on blood pressure control. 634 96

The renin-angiotensin system plays an important role in blood pressure homeostasis, but the contribution of the type 2 angiotensin II receptor (AT2R) is still unclear. The reports that the AT2R gene has been mapped to the X chromosome in human and rat and the previous report of a gene, Bp3, on the X chromosome responsible for an increase in blood pressure have suggested that the rat AT2R gene (Agtr2) could be this gene. To elucidate whether Agtr2 is Bp3, Agtr2 was cloned. A simple sequence repeat in the 3'-flanking region of this gene was identified and used as a genetic marker to map Agtr2 to the X chromosome at 18.1 cM distal to the androgen receptor locus. This map position is outside the confidence interval reported for Bp3, demonstrating that Agtr2 cannot be Bp3. However, these data will enhance the research into the AT2R biology as well as the study of the X chromosome.
Hypertension 1995 Dec
PMID:Cloning, characterization, and genetic mapping of the rat type 2 angiotensin II receptor gene. 749 Jan 61

Activation of the renin-angiotensin system by sodium deficiency is associated with reciprocal changes in the expression of angiotensin II receptors in adrenal glomerulosa and vascular smooth muscle cells. The effects of dietary sodium changes on the expression of brain angiotensin receptor subtype 1 (AT1) mRNAs were examined in rats maintained on normal, low, and high sodium intake for 3 weeks. Plasma aldosterone and renin activity were elevated in rats maintained on a low salt diet compared with normal rats and were reduced in rats maintained on a high salt diet. These results are consistent with previous findings on the effects of altered dietary sodium on the renin-angiotensin system. The expression of AT1A and AT1B receptor subtype mRNAs was determined by quantitative reverse transcriptase-polymerase chain reaction during changes in sodium intake. The results revealed that sodium deprivation enhanced the expression of AT1B receptors in decorticated brains by 164% compared with high sodium intake. Conversely, high sodium diet increased the expression of AT1A receptors by 155% in the brain compared with low sodium intake. These data suggest that AT1A and AT1B receptors play reciprocal roles in central mechanisms for the control of fluid homeostasis. Further analysis of the molecular biology of angiotensin II receptor regulation in the brain may provide new insights into the interplay between the renin-angiotensin system and blood pressure regulation and also into the role of angiotensin II in the pathogenesis of essential hypertension.
Hypertension 1994 Jan
PMID:Regulation of angiotensin II receptors in rat brain during dietary sodium changes. 750 98

Besides its glomerular hemodynamic effects, nitric oxide (NO) inhibits platelet aggregation and mesangial cell proliferation, two mechanisms possibly involved in the pathogenesis of glomerulosclerosis (GS). Chronic NO synthase inhibition in the rat leads to marked arterial hypertension and promotes glomerular and interstitial injury, but only mild GS. In this study, NO synthase blockade by nitro-L-arginine methyl ester (L-NAME) was associated with 5/6 nephrectomy, a well-known model of GS. Sixty-eight adult male Munich-Wistar rats were distributed among four groups: SHAM (no renal ablation or drug treatment), NX (5/6 nephrectomy), NX+NAME (5/6 nephrectomy and chronic treatment with L-NAME, 5 mg/dL in drinking water) and NX+NAME+L (as in group NX+NAME but also receiving the angiotensin II receptor inhibitor Losartan potassium (L), 25 mg/dL in drinking water). One week after ablation, rats of Group NX showed moderate glomerular hypertension and hypertrophy. Although glomerular enlargement was also modest in Group NX+NAME, glomerular hypertension was particularly severe in this group. Both alterations were absent in Group NX+NAME+L. Only incipient glomerular and interstitial injury occurred at this phase. Three weeks after ablation, renal structural injury was still modest in Group NX. By contrast, Group NX+NAME exhibited marked GS, glomerular ischemic injury, interstitial expansion, and creatinine retention. Renal injury was largely prevented in Group NX+NAME+L. Tuft enlargement occurred in all groups but was most prominent in Group NX. NO synthase inhibition aggravates parenchymal injury and functional impairment in the remanent kidney by mechanisms that may involve glomerular hypertension and renin-angiotensin activation but that appear to be unrelated to glomerular enlargement.
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PMID:Chronic nitric oxide synthase inhibition aggravates glomerular injury in rats with subtotal nephrectomy. 753 72

Future directions in antihypertensive treatment will rely on our present experience with antihypertensive drugs, on new concepts of cardiovascular regulation and on novel antihypertensive agents. At present, we seek early detection of hypertension; treatment should focus on normalization of blood pressure, the reversal or prevention of left ventricular hypertrophy, associated coronary artery disease and on the prevention of, or reparation of, myocardial fibrosis and microangiopathy. Therefore, combination therapy is advisable in severe cases, and any monotherapy should focus on the pharmacological principles compatible with these goals. ACE inhibitors and calcium antagonists appear to meet these requirements. There are, in addition, novel drugs i.e. angiotensin II receptor antagonists and renin inhibitors, as well as therapeutic stimulation of endothelial nitric oxide by L-arginine, the inhibition of endothelin-1 mediated vasoconstriction, and potassium-channel openers. All are examined in this contribution to delineate the perspectives in antihypertensive therapy.
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PMID:Directions in antihypertensive treatment--our future from the past. 755 77

SB 203220, [(E)-alpha-[[2-butyl-1-[(4-carboxy-1-naphthalenyl)-methyl]-1H- imidazol-5-yl]-methylene]-2-thiophene-propanic acid], is a novel nonpeptide angiotensin II receptor antagonist with significant oral activity. In the present study, we compared the cardiovascular and renal effects of SB 203220 and captopril in rats with chronic renal failure induced by 5/6 nephrectomy. Preliminary studies indicated that SB 203220 (600 ppm in the diet) and captopril (250 mg/l in drinking water) significantly attenuated the pressor activity of exogenous angiotensin II and angiotensin I, respectively. After 5/6 nephrectomy, significant hypertension was observed such that at 6 weeks, systolic blood pressure had reached 176 +/- 9 mm Hg. Both SB 203220 (128 +/- 18 mm Hg) and captopril (131 +/- 7 mm Hg) significantly attenuated the hypertension. Urinary protein excretion increased progressively after renal ablation (from 7 to 124 mg/day), and this was attenuated by both SB 203220 (32 +/- 7 mg/day) and captopril (42 +/- 6 mg/day). Assessment of serum creatinine and urea nitrogen indicated that SB 203220 but not captopril resulted in maintenance of renal function, close to that observed in control rats. Both SB 203220 and captopril attenuated the renal and left ventricular hypertrophy associated with 5/6 nephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:SB 203220: a novel angiotensin II receptor antagonist and renoprotective agent. 756 92

The effects of TCV-116, a new non-peptide angiotensin II receptor antagonist, on systemic and renal hemodynamics were studied in conscious normotensive and renal hypertensive (2-kidney, 1-clip Gold-blatt type) dogs. When orally administered at 0.03 to 1.0 mg/kg, TCV-116 inhibited the pressor response to angiotensin II in conscious normotensive dogs in a dose-dependent fashion. The IC50 and IC100 values were 0.06 mg/kg and 0.86 mg/kg, respectively. TCV-116 at doses of 0.3 mg/kg and 1.0 mg/kg dose-dependently and persistently decreased systolic and diastolic blood pressure in both dogs with acute renal (hyperreninemic) and those with chronic renal (normoreninemic) hypertension. Even a high dose of TCV-116 (10 mg/kg, p.o.) increased effective renal plasma flow without affecting blood pressure or glomerular filtration rate in normotensive dogs. Furthermore, even at this high dose, TCV-116 did not reduce effective renal plasma flow or glomerular filtration rate in dogs with renal hypertension despite marked reduction in systemic blood pressure. The angiotensin converting enzyme inhibitor enalapril (10 mg/kg, p.o.) had renal hemodynamic effects similar to those of TCV-116. These findings indicate that TCV-116 has potent hypotensive effects not only in dogs with acute renal hypertension but also in those with chronic renal hypertension, but does not appear to adversely affect renal hemodynamics.
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PMID:Effects of the non-peptide angiotensin II receptor antagonist TCV-116 on systemic and renal hemodynamics in dogs with renal hypertension. 758 13


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