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

We studied the alpha- and beta-adrenoceptor activity and catecholamine and cAMP levels in 112 children and infants admitted to the hospital for diagnostic or interventional catheterization of tetralogy of Fallot, ventricular septal defects with or without hypertension, pulmonary stenosis, coarctation of the aorta, and various complex cyanotic congenital cardiac diseases and compared them with 14 children undergoing transcatheter occlusion of patent ductus arteriosus with insignificant left-to-right-shunts. The mean total platelet alpha-adrenoceptor density of the study population was elevated by 73%. Both the increases in acyanotic (p < 0.05) and cyanotic (p < 0.005) patients as well as the difference between the two groups (p < 0.01) were significant. Based on the congenital disease classification, the elevation in receptor density was also significant in all groups of patients, except coarctation of the aorta. On the other hand, the mean lymphocyte beta-adrenoceptor density was attenuated by 27%, showing significant difference between the acyanotic and the patent ductus arteriosus groups, but none between acyanotic and cyanotic or cyanotic and the patent ductus arteriosus groups. Among the congenital groups, only the left-to-right shunts and the pulmonary stenosis group showed significant (p < 0.05) decrease in beta-adrenoceptor density, whereas the affinity of all the groups toward [125I]iodocyanopindolol was hardly influenced. The plasma levels of all three catecholamines, norepinephrine, epinephrine, and dopamine, were elevated, but cAMP remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of sympathetic activity in children with various congenital heart diseases. 747 97

Prostaglandin E1 has been shown to induce a greater accumulation of cAMP in platelets from spontaneously hypertensive (SHR) than in platelets from normotensive (Wistar-Kyoto, WKY) rats (Circ. Res. 1978;43:583-591. Thromb. Res. 1988;49:5-21). This study was conducted to determine the mechanisms of increased platelet reactivity to PGE1 in hypertension. The number of PGE1 binding sites/platelet (WKY 280 +/- 8, SHR 287 +/- 5) as well as the Kd for WKY (105 +/- 11 nmol/L) and SHR (120 +/- 14 nmol/L) were found to be similar in WKY and SHR rats. PGE1-induced GTPase activity was determined using WKY and SHR platelet membranes. The basal GTPase activity was similar in WKY and SHR platelets. Incubation of membranes with PGE1 (3 mumol/L) for 1 min increased GTPase activity by 46% in WKY and by 806% in SHR. Incubation of platelets with 1.0 mmol/L IBMX (3-isobutyl-1-methyl-xanthine) for 4 min resulted in a 327 +/- 57% and 320 +/- 11% increase in cAMP in WKY and SHR platelets, respectively. In other experiments, incubation of platelets with 3, 10 and 100 mumol/L forskolin, induced similar increases in cAMP levels in WKY (103 +/- 12%, 530 +/- 42%, 784 +/- 41%) and SHR (111 +/- 13%, 461 +/- 18%, 756 +/- 28%) platelets. These data lead us to suggest that the greater accumulation of cAMP induced by PGE1 in SHR than in WKY platelets is linked with altered PGE1-receptor mediated signal transduction at the G-protein level.
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PMID:Increased platelet reactivity to prostaglandin E1 in hypertension is linked with altered signal transduction. 750 93

Although the biochemical properties of soluble guanylate cyclase (sGC) have been extensively studied, little is known about the regulation of gene expression of sGC subunits by second messengers. cAMP analogues and elevating agents have been previously shown to alter gene expression in vascular cells. The aim of the present study was to investigate the effects of cAMP-elevating agents on sodium nitroprusside-stimulated sGC activity and to correlate activity changes with mRNA and protein levels in cultured rat aortic smooth muscle cells. Pretreatment of cells with 50 to 1000 mumol/L isobutylmethyl-xanthine or 0.01 to 10 mumol/L forskolin led to a time- and concentration-dependent decrease in sodium nitroprusside-induced cGMP accumulation, first evident after 3 hours of pretreatment with forskolin and 6 hours of pretreatment with isobutylmethylxanthine. Incubation of cells with a protein kinase A-selective inhibitor (H89 or KT 5720) partially or fully prevented the downregulation in sodium nitroprusside-induced cGMP accumulation caused by cAMP-elevating agents. Quantification of reverse transcriptase-polymerase chain reaction products by high-performance liquid chromatography revealed that mRNA for both alpha1- and beta1-subunits of sGC were decreased in cells pretreated with isobutylmethylxanthine and forskolin but not with dideoxyforskolin (inactive analogue). Moreover, protein levels for the sGC alpha1 subunit of cells pretreated with isobutylmethylxanthine and forskolin but not with dideoxyforskolin were decreased as indicated by Western blot analysis. These data indicate that cAMP-elevating agents decrease sGC activity, possibly by decreasing mRNA or protein levels or both.
Hypertension 1995 Oct
PMID:Regulation of vascular smooth muscle soluble guanylate cyclase activity, mRNA, and protein levels by cAMP-elevating agents. 755 33

In order to study the effect of dihydroxyacetophenone (DHAP) on pulmonary hemodynamics and its relationship to plasma ANP as well as cAMP/cGMP level in chronic obstructive pulmonary disease (COPD), 11 COPD patients were examined with the right heart catheterisation, and the plasma ANP and cAMP/cGMP were measured with radioimmunoassay at the same time. The results showed that intravenous given DHAP 640 mg could decrease mean pulmonary arterial pressure, pulmonary vascular resistance and systemic vascular resistance (P < 0.05), but increase the cardiac output from 4.10 +/- 1.08 L/min to 5.13 +/- 1.19 L/min (P > 0.05) and not affect systemic arterial pressure (P > 0.05) as well as blood gas analysis; it also reduce the plasma ANP and cGMP level from 0.73 +/- 0.42 pg/ml to 0.41 +/- 0.33 pg/ml (P < 0.01) and from 9.82 +/- 5.75 pm/ml to 8.01 +/- 4.80 pm/ml (P < 0.05) respectively, but did not affect the plasma cAMP level (P > 0.05). It is suggested that DHAP may relax pulmonary vessels by regulating the ratio of cAMP to cGMP, and the lowering of plasma ANP level might be a secondary reaction. So we consider that DHAP is a fast-acting, safe and potential drug in treating pulmonary arterial hypertension by COPD.
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PMID:[Effects of dihydroxyacetophenone on pulmonary hemodynamics and plasma ANP as well as cAMP/cGMP level in patients with chronic obstructive pulmonary disease]. 764 23

The purpose of this study was to observe the abnormalities of calcium transport of cultured arterial smooth muscle cells (ASMC) in both prehypertensive and hypertensive SHR and their control WKY rats. The changes in cAMP, ANG II and CaM contents in ASMC were also studied. The results indicated that the Ca2+ influx in ASMC of prehypertensive SHR was increased compared with that of the control, although the value of that in hypertensive SHR was higher significantly more than that of the prehypertensive rat, but there was no significant difference between them. On the other hand, the Ca2+ efflux in ASMC of prehypertensive SHR was decreased compared with that of WKY rats. A more seriously decreased efflux value was found in hypertensive SHR. The cAMP and CaM content were higher than those in WKY rats. In addition, ANG II content in ASMC had a direct bearing on blood pressure, showing a marked difference between prehypertensive and hypertensive SHR. The disturbance of transmembrane Ca2+ transport in ASMC of hypertensive rats appears to be related to genetic defect and the changes of cAMP contents might play a role in membrane Ca2+ transport in ASMC during the development of hypertension. Furthermore the level of arterial ANG II may be related to the elevation of blood pressure in hypertension.
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PMID:[The disturbance of Ca2+ transport and the changes of some relative factors in arterial smooth muscle cells from spontaneously hypertensive rats with different age]. 765 89

The involvement of adenosine 3',5'-cyclic monophosphate (cAMP) in the stimulation of ventricular protein synthesis by aortic hypertension or adrenergic agonists in the adult rat heart was investigated. In either the retrogradely or anterogradely perfused heart, aortic hypertension increased protein synthesis rates by up to 19%. However, no changes in cAMP concentrations or in cAMP-dependent protein kinase activity ratios could be detected either at early (< 5 min) or late (90 min) time points. Although isoproterenol, 3-isobutyl-1-methylxanthine, or forskolin raised cAMP concentrations (by up to 4.5-fold) and cAMP-dependent protein kinase ratios (by up to 4-fold), protein synthesis rates were not increased; however, under some perfusion conditions, glucagon did stimulate protein synthesis by 25%. Epinephrine stimulated protein synthesis by up to 32%, an effect that was not prevented by propranolol. Phenylephrine also stimulated protein synthesis, an effect that was prevented by prazosin but was unaffected by yohimbine. These findings implicate the alpha 1-adrenoceptor in the regulation of cardiac protein synthesis. Because changes in adenine nucleotide concentrations were similar in hearts perfused with epinephrine or with the agents that raised cAMP, it is unlikely that adenine nucleotide depletion is responsible for the failure to observe effects of the latter group of agents on protein synthesis. Although isoproterenol or forskolin raised cAMP concentrations in isolated ventricular cardiomyocytes where ATP depletion was minimal, neither stimulated protein synthesis. alpha 1-Adrenergic agonists stimulate phosphoinositide hydrolysis in the heart (Brown, J. H., I. L. Buxton, and L. L. Brunton. Circ. Res. 57:532-537, 1985). Aortic hypertension doubled the rate of phosphoinositide hydrolysis in the perfused heart. We suggest that the phosphoinositide-linked signal transduction pathway is more likely to be involved in stimulation of cardiac protein synthesis by hypertension or adrenergic agonism than the adenylyl cyclase/cAMP-linked pathway.
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PMID:cAMP and protein synthesis in isolated adult rat heart preparations. 769 91

The development of hypertension in the spontaneously hypertensive rat (SHR) is associated with renal dysfunction and vasoconstriction. The kidneys of young SHRs exhibit exaggerated reactivity to angiotensin II (Ang-II) and attenuated responses to vasodilators that normally activate the cAMP signal to buffer hormone-induced vasoconstriction. The present study investigates the mechanism(s) responsible for this abnormality in activation of the cAMP second-messenger pathway in hypertensive animals. Renal vascular reactivity was assessed in 7-week-old anesthetized SHRs and normotensive Wistar-Kyoto rats. The animals were pretreated with indomethacin to block prostanoid production throughout an experiment. Ang-II was injected into the renal artery either alone or mixed with the vasodilator fenoldopam, a dopamine-receptor agonist. These two opposing vasoactive agents were administered before and during intrarenal infusion of NaF or cholera toxin, two activators of G proteins that stimulate cAMP production. The results show that Ang-II reduced renal blood flow by 45% in both strains. In Wistar-Kyoto rats, fenoldopam reduced the Ang-II-induced decrease in renal blood flow from -45% to -30%. This protective effect of fenoldopam was increased further during infusion of NaF or cholera toxin (-18% or -19% decrease in renal blood flow). In SHRs, fenoldopam failed to attenuate Ang II-mediated vasoconstriction (-45% vs. -44%). In contrast, fenoldopam effectively blunted the Ang-II-induced vasoconstriction when it was given concurrently with NaF or cholera toxin (-27 or -31% decrease in renal blood flow). These findings provide evidence for defective interaction between receptor coupling and activation of guanine nucleotide stimulatory factor proteins in the renal microcirculation of 7-week-old SHRs. Such a deficiency could play an important role in renal dysfunction associated with the development of genetic hypertension.
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PMID:Defective G protein activation of the cAMP pathway in rat kidney during genetic hypertension. 770 50

With the development of subtype specific angiotensin II (Ang II) receptor antagonists and their introduction into the treatment of heart failure and hypertension, the regulation of the Ang II receptor with its subtypes AT1 and Ang T2 gains clinical importance. In cell cultures, the number of surface AT1 is clearly down-regulated by Ang II exposure. Down-regulation can be due to reversible internalization, to phosphorylation and to reduced synthesis and involves protein kinase C and phospholipase C mediated pathways. In this respect, the AT1 behaves as a typical G-protein coupled receptor. Aldosterone, cAMP, norepinephrine and extracellular glucose concentrations can contribute to AT1 regulation. There are very few data regarding the regulation of the subtype AT2, indicating modulation by a number of growth factors and by Ang II. In whole animal models receptor regulation deviates partially from cell cultures. In the rat, the two subtypes AT1A and AT1B are differentially regulated and the expression of subtypes is organ specific. In most experiments, including our own experiences, the AT1, in the adrenals was up-regulated by Ang II infusion and down-regulated by angiotensin converting enzyme inhibitors (ACEI) or Ang II receptor antagonists. Differing effects were observed in other organs. In humans, a number of studies seeking an association between Ang II levels, Ang II receptor regulation and physiological events have been conducted in platelets. In pregnant women, a negative correlation between plasma Ang II levels and Ang II binding and an association between receptor regulation and pregnancy-induced hypertension has been described.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of the angiotensin receptor subtypes in cell cultures, animal models and human diseases. 771 21

Although PTH and PTH-related protein (PTHrP) are vasodilators, prolonged exposure to elevated levels of PTH is often associated with hypertension. We investigated the effects of prolonged incubation with PTH or PTHrP on arterial segments and cultured vascular smooth muscle cells (VSMC). PTH or PTHrP transiently relaxed precontracted arterial segments within 10 min. Additional PTH or PTHrP added after 40-min exposure to these peptides had little effect on vascular tone, whereas forskolin, isoproterenol, isobutylmethyl-xanthine, or acetylcholine were still potent. In fura 2-loaded VSMC, 5-min incubation with PTH or PTHrP attenuated angiotensin II (Ang II)-induced calcium mobilization, an effect that was reduced by preincubation of VSMC with PTH for 1.5 h. Similarly, 1.5-h preincubation with PTH or PTHrP decreased the cAMP response to these peptides but not to forskolin or NaF. Ang II potentiated the cAMP response to PTH and PTHrP but was also subject to desensitization. Nle8, 18Tyr34 bovine PTH(3-34) amide did not desensitize vascular tissue to PTH or PTHrP. Our results suggest that homologous desensitization to PTH or PTHrP in vascular tissue requires receptor stimulation, occurs proximal to G stimulatory protein, and impairs attenuation of calcium mobilization by PTH or PTHrP. This may be a mechanism by which vasodilator effects of these peptides are decreased with prolonged elevation of PTH levels.
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PMID:Desensitization of vascular tissue to parathyroid hormone and parathyroid hormone-related protein. 775 Apr 71

We have previously shown that the human adrenocortical H295R cell line expresses the type 1 angiotensin II receptor (AT1-R) and that expression of this receptor is downregulated at the level of mRNA by forskolin or dibutyryl-cAMP as well as by angiotensin II (Ang II). In this study we examine the effects of K+ on both AT1-R mRNA and receptors, as monitored through 125I-Ang II binding in the presence of PD 123319. After treatment with a maximal stimulatory steroidogenic dose of K+ (14 mmol/L), H295R cells showed an increase in cytosolic free Ca2+ from 113 to 212 nmol/L. Unlike the effects of Ang II, this increase could be abolished by pretreatment with the Ca2+ channel antagonist nifedipine (1 mumol/L). AT1-R mRNA levels also fell in response to elevated extracellular K+ in a dose-dependent (Kd, 9 mmol/L; maximal fall in message at 12 mmol/L) and time-dependent (maximum 50% at 12 hours) manner. The change in AT1-R mRNA level was less rapid than that in response to activation of phosphoinositidase C by Ang II or adenylyl cyclase by forskolin or by dibutyryl-cAMP. Unlike the action of Ang II but similar to the action of forskolin or dibutyryl-cAMP, the action of K+ was sustained. Changes in mRNA level in response to treatment with K+, Ang II, or dibutyryl-cAMP were also paralleled by changes in 125I-Ang II binding in each case.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Jun
PMID:Potassium negatively regulates angiotensin II type 1 receptor expression in human adrenocortical H295R cells. 776 52


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