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

There is evidence that atrial natriuretic factor (ANF) has an action in the inner medullary collecting duct. In addition, the prehypertensive Dahl salt-sensitive (S) rat has an intrinsic tendency toward less natriuresis than the Dahl salt-resistant (R) rat has when challenged with ANF. To test the hypothesis that renal papillary collecting tubule cells from prehypertensive S rats might be genetically less responsive to ANF, S and R cells were grown in culture and studied for responsiveness to ANF by measurement of cyclic nucleotide responses. There was a concentration-dependent effect of ANF on renal papillary collecting tubule cell synthesis of intracellular cyclic guanosine 3',5'-monophosphate (cGMP) in both strains. However, the S cells were hyporesponsive compared with the R cells (p less than 0.002, by analysis of variance). Likewise, in response to Na nitroprusside, the S cells were hyporesponsive compared with the R cells as measured by intracellular cGMP accumulation (p less than 0.03, by analysis of variance). Arginine vasopressin stimulated intracellular cAMP equally in both strains. Also, ANF equally enhanced intracellular cGMP in glomerular mesangial cells from S and R rats, indicating possible specificity of the reduced responsiveness to ANF to the distal nephron of S rats. Plasma ANF levels had a slight tendency to be higher in prehypertensive S rats than in R rats (p = 0.088, by t test). These results suggest that the papillary collecting duct of Dahl S and R rats may differ in guanylate cyclase activity. This difference may partially explain the impaired natriuretic responses of S rats and could represent a factor contributing to the development of salt-sensitive hypertension.
Hypertension 1987 Jul
PMID:Papillary collecting tubule responsiveness to atrial natriuretic factor in Dahl rats. 303

Phosphoinositide hydrolysis is an integral step in the activation of vascular smooth muscle by angiotensin II. Sequential phospholipase C-mediated hydrolysis of the polyphosphoinositides and phosphatidylinositol in cultured vascular smooth muscle cells stimulated with angiotensin II results in a coordinated series of biochemical events: a transient formation of inositol trisphosphate associated with calcium mobilization, and a biphasic, sustained formation of diacylglycerol associated with activation of protein kinase C and cytosolic alkalinization. The initial, rapid phase and the sustained phase of the angiotensin II response appear to be differentially controlled. Formation of inositol trisphosphate and mobilization of calcium are attenuated by activation of protein kinase C. Sustained diacylglycerol formation is promoted by cytosolic alkalinization, and appears to require cellular processing of the angiotensin II-receptor complex. Calcium and cyclic guanosine 3',5'-monophosphate do not appear to regulate phospholipase C-mediated phosphoinositide hydrolysis in vascular smooth muscle. Thus, regulation of angiotensin II-stimulated second messenger generation in vascular smooth muscle is complex, perhaps involving protein kinase C activation, changes in intracellular pH, and processing of the angiotensin II-receptor complex.
Hypertension 1987 Jun
PMID:Angiotensin II stimulation of vascular smooth muscle phosphoinositide metabolism. State of the art lecture. 303 1

Many vasoactive agents stimulate release of an endothelium-derived relaxing factor (EDRF). EDRF stimulates cyclic guanosine 3',5'-monophosphate (cGMP) accumulation and relaxation of vascular smooth muscle in a manner similar to that produced by sodium nitroprusside. Endothelium and vascular smooth muscle were isolated from porcine, bovine, and rat thoracic aorta. The capacity of sodium nitroprusside to stimulate cGMP accumulation in cultured bovine, porcine, and rat vascular smooth muscle was found to increase with time in culture to a maximum of 12 to 14 days after plating. In addition, bovine and porcine vascular smooth muscle, but not rat vascular smooth muscle, lost the sodium nitroprusside-stimulated cGMP response after the fifth passage. Cultured endothelial cells did not respond to endothelium-dependent vasodilators or sodium nitroprusside with increased cGMP levels. Vascular smooth muscle cells responded only to sodium nitroprusside. Mixed cultures of porcine and bovine endothelium and vascular smooth muscle and bovine endothelium and rat vascular smooth muscle responded to endothelium-dependent vasodilators with increased cGMP levels. Short-term (4 hours) coculture experiments using bovine endothelium grown on microcarriers to assess the need for long-term contact between the two cell types produced similar results. Release of EDRF from bovine endothelium was studied by loading endothelium-covered microcarrier beads into a column superfused with physiological buffer. Treatment of the column with bradykinin, the calcium ionophore A23187, melittin, and arachidonate released EDRF from the column as measured by cGMP changes in denuded aortic rings and vascular smooth muscle cells and by relaxation of rings when bathed in column effluent. The time course of cGMP changes and relaxation were similar and could be reversed by hydroquinone.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1987 Jun
PMID:Endothelium-derived relaxing factor in cultured cells. 303 2

The relaxation of phenylephrine-contracted blood vessels by acetylcholine, nitroprusside, or atrial natriuretic factor has been linked to elevations in cyclic guanosine 3',5'-monophosphate (cGMP). Also, 8-bromo-cGMP can induce vascular relaxation in isolated vascular smooth muscle contracted with phenylephrine. We determined whether these cGMP-dependent vasodilators could relax isolated rat aortas contracted with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. cGMP was measured by radioimmunoassay. Acetylcholine, nitroprusside, and atrial natriuretic factor induced relaxation in vascular smooth muscle contracted by 12-O-tetradecanoylphorbol-13-acetate. These relaxation responses were accompanied by elevations of cGMP. However, the sensitivity to these vasodilators was markedly decreased in phorbol ester-contracted vessels compared to phenylephrine-contracted vessels. Nifedipine and superoxide dismutase induced small but significant relaxations in phorbol ester-contracted vessels; however, blood vessels contracted with phenylephrine and phorbol ester relaxed completely with papaverine. There was a marked decrease in sensitivity to 8-bromo-cGMP in phorbol ester-treated vessels compared to phenylephrine-contracted vessels. Contractions induced by phorbol ester were not inhibited by amiloride or chlorpromazine. Also, following incubation in potassium-free salt solution, vessels incubated with phenylephrine or phenylephrine and phorbol ester underwent similar relaxations when exposed to potassium chloride. The contractile state induced by phorbol ester has decreased sensitivity to cGMP-dependent vasodilators. This may be due to nonspecific effects of the phorbol ester or to the mechanism by which protein kinase C activation maintains vascular tone.
Hypertension 1987 Jun
PMID:Phorbol ester, vascular relaxation, and cyclic guanosine 3',5'-monophosphate. 303 7

Plasma levels of atrial natriuretic peptide (ANP) were measured in 32 untreated subjects with essential hypertension and in 31 patients undergoing long-term treatment with beta-blockers. Patients receiving beta-blockers had significantly higher mean plasma ANP levels (72.0 +/- 36.0 [SD] pg/ml) than did untreated hypertensive subjects (39.8 +/- 15.8 pg/ml; p less than 0.01) and healthy normotensive controls (33.9 +/- 16.6 pg/ml; n = 61, p less than 0.01), while the mean plasma ANP concentration in untreated hypertensive subjects was not statistically different from that in control subjects. Administration of atenolol, 50 mg/day, for 4 weeks to 10 untreated subjects resulted in a significant (p less than 0.001) rise in plasma ANP levels (from 38.8 +/- 9.5 to 68.7 +/- 20.6 pg/ml). In 31 patients undergoing long-term treatment with beta-blockers, multivariate regression analysis revealed that age, pretreatment mean blood pressure, and plasma concentration of cyclic 3',5'-guanosine monophosphate (cGMP) were significant predictors of plasma ANP levels. These results suggest that beta-adrenergic receptor blockade in patients with essential hypertension elevates plasma ANP levels with a concomitant rise in cGMP concentrations, and that increased ANP in plasma may play a role in the compensatory mechanism that operates in response to beta-adrenergic receptor blockade.
Hypertension 1987 Aug
PMID:Effect of beta-adrenergic receptor blockade on atrial natriuretic peptide in essential hypertension. 303 46

Endothelium-derived relaxing factor (EDRF) is a labile humoral agent released by vascular endothelium that mediates the relaxation induced by some vasodilators, including acetylcholine and bradykinin. EDRF also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to vascular endothelium. These actions of EDRF are mediated through stimulation of the soluble guanylate cyclase and the consequent elevation of cyclic guanosine 3',5'-monophosphate. EDRF has been identified as nitric oxide (NO). The pharmacology of NO and EDRF is indistinguishable; furthermore, sufficient NO is released from endothelial cells to account for the biological activities of EDRF. Organic nitrates exert their vasodilator activity following conversion to NO in vascular smooth muscle cells. Thus, NO may be considered the endogenous nitrovasodilator. NO is synthesized by vascular endothelium from the terminal guanido nitrogen atom(s) of the amino acid L-arginine. This indicates the existence of an enzymic pathway in which L-arginine is the endogenous precursor for the synthesis of NO. The discovery of the release of NO by vascular endothelial cells, the biosynthetic pathway leading to its generation, and its interaction with other vasoactive substances opens up new avenues for research into the physiology and pathophysiology of the vessel wall.
Hypertension 1988 Oct
PMID:The discovery of nitric oxide as the endogenous nitrovasodilator. 304 40

The role of endothelial cells in modulating the vascular smooth muscle tone in aging and hypertension was examined. Results from in vitro pharmacological studies indicate that vasodilations of rat arteries induced by several dilator agents, such as nitrovasodilators, decrease with advancing age and experimental hypertension. These diminished dilator responses to nitrovasodilators however were not observed in arteries with endothelial cells removed. Furthermore, 8-bromo-cGMP-induced relaxations were not different between arteries with and without endothelial cells and were not affected by hypertension. It appears that the diminished vasodilator responses in aging and hypertension is not initially due to defects in vascular smooth muscle but rather due to an altered modulatory function of the endothelial cells. At different ages and under different pathological conditions, such as hypertension, the ratio of production and/or activities of endothelium-derived relaxing factors and endothelium-derived constrictor factors may vary, and therefore directly or indirectly affect the production of cGMP and smooth muscle tone.
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PMID:Altered endothelial modulation of vascular tone in aging and hypertension. 359 76

In the aortas and mesenteric arteries from spontaneous hypertensive rats and in the aortas from stress- and desoxycorticosterone-acetate-hypertensive rats, the intracellular cGMP: cAMP ratios were significantly elevated when compared to the ratios in the aortas of the respective controls. Decreases in the intracellular cAMP or cGMP levels were consistently associated with increased activity of the cyclic-nucleotide-specific low K(m) phosphodiesterase (3':5'-cAMP 5' nucleotidohydrolase, EC 3.1.4.17). Increases in intracellular cGMP levels were associated with elevated guanylyl cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity. Furthermore, adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity was less sensitive to stimulation by the beta-adrenergic stimulant isoproterenol in both the aortas and the hearts of the hypertensive animals. These changes could provide the biochemical basis for the (a) increased vascular smooth muscle tone and peripheral resistance observed in these animals, (b) increased reactivity to norepinephrine, and (c) decreased ability of aortas from hypertensive rats to relax. The presence of these same effects in different etiologic types of hypertension indicates that this aberration in cyclic nucleotide metabolism may represent a common metabolic defect basic to the hypertensive syndrome irrespective of etiology.
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PMID:Aberrations of cyclic nucleotide metabolism in the hearts and vessels of hypertensive rats. 415 74

An acute hot stress caused a sharp increase in plasma cyclic AMP and cyclic GMP in both spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). This hot stress-induced increase in plasma cyclic AMP was observed even after chemical sympathectomy elicited by 6-hydroxydopamine or depleting the catecholamine stores in adrenergic neurons by tyramine or reserpinization, but was no longer observable after beta-adrenergic blockade by propranolol, blockade of autonomic ganglia by hexamethonium, adrenodemedullation or anesthesia by pentobarbital. These results indicate that the initial stimulation of the central nervous system evoked the release of catecholamines from the adrenal medulla which could activate adenylate cyclase via the stimulation of beta-adrenoceptors on the cell surface. The increment of plasma cyclic GMP was not influenced by prior blockade of the peripheral autonomic nervous system, but was totally abolished by pentobarbital, indicating that cyclic GMP generated within the central nervous system in response to the hot stress would be directly related to its increase in the peripheral blood stream. The plasma cyclic AMP and cyclic GMP responses were greater in adult SHR than in young SHR and young and matured WKY. The predominant response of plasma cyclic AMP might be due to a greater release of catecholamine from the adrenal medulla in matured SHR. The hyperresponse of plasma cyclic GMP in adult SHR remains to be fully elucidated. The increased cyclic nucleotide responses in SHR might be an important factor in the maintenance of hypertension.
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PMID:Plasma cyclic nucleotides in spontaneously hypertensive rats: hyperresponse to acute hot stress. 608 98

The transplantable pituitary tumor MtT-F4 secretes several pituitary hormones in Fisher rats, resulting in severe cardiovascular disease with a mineralocorticoid type of hypertension and hyperlipidemia. The mineralocorticoid-dependent hypertension possesses particular characteristics in humans and animals. It was of interest to study cyclic nucleotides and platelet aggregation in the Fisher rat with an MtT-F4 tumor in order to evaluate the type of abnormalities in this form of hypertension. The effect of administration of an anti-hyperlipidemic agent (clofibrate) was also evaluated. The animals bearing the tumor showed anomalies of platelet aggregation induced by the divalent cation ionophore A 23187, in that there was an apparent enhanced change in shape and a decreased rate of aggregation. Although the basal concentrations of cyclic nucleotides were normal, as were the increases in cyclic GMP induced by epinephrine, cyclic AMP concentrations increased less (about 2.7-fold) in response to PGE1 than in control Fisher rats (about 6-fold). A decreased stimulation of adenylate cyclase activity by PGE1 was observed in platelets of tumor-bearing rats. The administration of clofibrate to sham-operated animals somewhat lowered the increase of cyclic AMP in response to PGE1. In tumor-bearing animals, clofibrate considerably reduced plasma lipids, blood pressure and the degree of abnormalities in platelet aggregation and cyclic AMP in platelets. Thus, the abnormalities of platelet aggregation and regulation of cyclic nucleotides in the mineralocorticoid-type of hypertension induced by MtT-F4 were opposite to those found previously in spontaneous hypertension in rats. Hyperlipidemic and hypertensive rats with MtT-F4 tumor may provide a useful model for the study of the relatioship between hyperlipidemia and hypertension.
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PMID:Cyclic nucleotides and platelet aggregation in hypertensive rats with ectopic pituitary tumor. 624 46


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