Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemodynamic changes observed in patients with the "hyperkinetic" form of borderline (labile) essential hypertension (BEH) could be related to the hyperresponsiveness of cardiac beta-adrenergic receptors to catecholamines. The isoproterenol-induced increase in plasma cyclic adenosine 3':5'-monophosphate (cAMP) reflects the response of adenylate cyclase to beta-adrenergic stimulation, whereas a non-beta-receptor-mediated increase occurs with the administration of glucagon. Both substances were infused into 13 control subjects and 14 patients with the hyperkinetic form of BEH before and after propranolol administration. Baseline plasma cAMP concentrations were comparable in both groups. After 30 minutes of isoproterenol infusion (20 ng/kg per min) a significantly higher increase in plasma cAMP and heart rate and a smaller decrease in diastolic blood pressure were seen in this type of BEH than in control subjects. The increase in plasma cAMP and in heart rate correlated positively when all subjects were considered together. Propranolol abolished hemodynamic and humoral responses to a similar degree in both groups. The plasma cAMP responses to glucagon (200 ng/kg per min) were slightly lower in our patients with BEH than in control subjects and were not suppressed by propranolol. The data are compatible with a hyperreactivity of the beta-adrenergic receptors or of the adenylate cyclase or both in hyperkinetic BEH and could correspond to the previously observed exaggerated beta-adrenergic drive to the heart in this type of hypertension. The non-beta-receptor-mediated rise in plasma cAMP (glucagon), however, remains comparable in control subjects and BEH.
...
PMID:Plasma cyclic adenosine 3':5'-monophosphate response to isoproterenol and glucagon in hyperkinetic borderline (labile) hypertension. 17 67

This study was designed to clarify the state of beta-adrenergic signal transduction and the disordered level of its transduction in hypertensive hearts, using myocardium from spontaneously hypertensive rats (SHR) as a generic model of essential hypertension. Beta-adrenergic receptor binding sites and dissociation constants in the extracted membranes of adult (70-100 days of age) SHR heart were not significantly different from those of Wistar-Kyoto (WKY) rats, the non-hypertensive control. The adenylate cyclase activities stimulated by isoproterenol with GTP, NaF and forskolin were significantly higher in SHR compared to those in WKY. To determine whether differences in signal transduction are natural or are a result of hypertension, we evaluated chronotropic responses in cultured cells of fetal hearts which had not been exposed to hypertension. Fetal cardiac muscle cells of SHR were more sensitive than WKY to isoproterenol stimulation over a wide concentration range. However, there were no statistically significant differences between these two strains with respect to the density of binding sites. These results suggest that in the transduction of adrenergic signals, alterations distal to the beta-receptors are present in the adult hearts of hypertensive rats, and, that the adrenergic signal transduction is already exaggerated in the pre-hypertensive fetal stage.
...
PMID:Enhanced myocardial adenylate cyclase activity in spontaneously hypertensive rats. 131 19

Previous assessment of beta-adrenoceptor function has shown alterations in essential hypertension (EH). In the present study, we compared lymphocyte beta-adrenoceptor density (Bmax) and adenylate cyclase (AC) activity stimulated by l-isoproterenol, Gpp(NH)p, Gpp(NH)p + l-isoproterenol, and forskolin in 46 patients with EH and in 17 normotensive subjects. The patients with EH were divided into two subgroups, one with left ventricular myocardial mass (LVMM) less than 200 g and the second with LVMM greater than 200 g (according to Teichholz' formula). There were no significant differences in Bmax or in AC activity [basal and stimulated by Gpp(NH)p and forskolin] between the patients and the normotensive subjects. Adenylate cyclase activity stimulated by l-isoproterenol was reduced (% from basal AC) in the patients (P less than .05), and Bmax was increased only in the patients with left ventricular hypertrophy (P less than .05). There were no differences in AC activity between the two patient subgroups, and Bmax and AC activity did not correlate with blood pressure in either the patients or the normotensive subjects. Correlations were found between Bmax and LVMM (r = 0.38, P less than .02) and between Bmax and interventricular septum thickness (r = 0.412, P less than .02) among the patients. Thus, beta-adrenergic-mediated AC sensitivity to catecholamines is reduced in patients with EH and may represent a generalized defect in beta-receptor function in EH. Increased Bmax is likely to characterize more pronounced involvement of the target organs in the pathologic process associated with EH than is a higher blood pressure level.
...
PMID:Alteration of beta-adrenoceptor function in hypertensive patients with different degrees of left ventricular hypertrophy. 132 40

1. To estimate the role of renal dopaminergic mechanisms in the pathogenesis of hypertension, patients with essential hypertension and animal models of hypertension were investigated. 2. Impaired dopaminergic activity in kidneys for natriuresis was observed in patients with 'salt-sensitive' hypertension and with low-renin hypertension. 3. Decreased dopaminergic activity in kidneys was observed in the Dahl S-rats without salt loading. 4. In spontaneously hypertensive rats, renal dopamine synthesis was enhanced whereas there was a decrease of adenylate cyclase activity in renal tubules. 5. Demonstration of impaired dopaminergic mechanisms in kidneys of human and animal hypertension suggests that renal dopaminergic mechanisms play an important role in development of hypertension.
...
PMID:Role of dopaminergic mechanisms in the kidney for the pathogenesis of hypertension. 209 77

Various physiological changes of platelets and the vascular smooth muscle cell are intimately related. For this reason, in addition to the number of features in common between platelets and vascular smooth muscle and the increased risk for thromboembolic complication in essential hypertension, the platelet was used as an experimental model for the investigation of calcium-dependent functional anomalies associated with hypertension. It is demonstrated, by a sequential analysis of receptor and postreceptor events, that platelets in hypertension exhibit (a) a greater adenylate cyclase-activation and c-AMP-accumulation response to PGE1, (b) an enhanced epinephrine-induced phosphorylation response, and (c) an increased shape change sensitivity to serotonin and epinephrine. The anomalies in these calcium-dependent processes are linked to elevated free calcium concentrations in platelets from hypertensive subjects.
...
PMID:Platelets and hypertension. 241 69

The sympathetic nervous activity contributes to the pathophysiology of essential hypertension in an early phase and in younger patients mainly through increased beta-adrenoceptor-mediated functions and in a later phase and in older patients in whom beta-adrenoceptor-mediated functions are blunted, through increased alpha-adrenoceptor-mediated and calcium-influx-dependent vasoconstriction. Intracellular free calcium concentration is elevated in platelets of hypertensive patients and relates directly to the degree of their blood pressure, likely reflecting increased intracellular calcium concentration in vascular smooth muscle cells. A sympathetic factor is suggested further by the enhanced alpha 1-and alpha 2-adrenoceptor-mediated and calcium influx-dependent, vasoconstriction both of which are normalized by antihypertensive treatment in parallel with a normalization of intracellular free calcium and of the increased adrenaline sensitivity of platelets. The higher sensitivity to adrenaline for thrombin-induced calcium increases in platelets of hypertensive patients indicates potentiation of calcium influx (and mobilization from intracellular stores) by adrenaline, a mechanism that is mediated by alpha 2-adrenoceptors. As this effect is more pronounced in younger patients, increased adenylate cyclase sensitivity may prevail in the early and alterations in calcium influx-dependent mechanisms in the later phase of essential hypertension. The transition into a hypertensive state with reduced-reflex cardiovascular counterregulation codetermines the antihypertensive effectiveness of calcium antagonists in these patients.
...
PMID:Adrenoceptors, calcium, and vasoconstriction in normal and hypertensive humans. 241 75

The plasticity of cellular Ca2+ control and the events regulated by [Ca2+]i and other messengers make it difficult to assign causative or consequential roles to deranged platelet Ca2+-linked processes in the pathophysiology of essential hypertension. Our studies in human platelets support an underlying membrane pathology as being causative since observed derangements including partial membrane depolarization and enhanced calcium influx, enhanced hormone responsiveness and coupling to adenylate cyclase, increased phosphoinositide metabolism, as well as stimulated Ca2+-ATPase extrusion activity are membrane associated systems. Modification of phosphoinositide metabolism may be a key factor accounting for the multifaceted membrane abnormalities and eventually contribute to the elevated cytosolic [Ca2+]i concentration in essential hypertension. Whether these membrane abnormalities can also be found in human smooth muscle cells has yet to be determined.
...
PMID:Abnormal cellular calcium regulation in essential hypertension. 243 18

Effects of dynamic exercise on lymphocyte beta 2-adrenoreceptor density (BARD) and adenylate cyclase activity (ACA) basal and stimulated by isoproterenol (I). Gpp(NH)p, Gpp(NH)p+I, and forskolin (F), on plasma adrenaline and noradrenaline levels, renin activity (PRA) were compared in 6 healthy donors and 12 patients with essential hypertension (EH). Acute stimulation of sympathetic activity by dynamic exercise leads to a rapid increase in lymphocyte BARD in normotensive and hypertensive subjects. The rise in BARD was accompanied by a significant increase in lymphocyte basal ACA in normotensive subjects, but not hypertensive patients. In patients with EH, basal ACA changed after exercise according to their renin status: patients with low baseline PRA showed a decrease in basal ACA after exercise, whereas patients with normal baseline PRA showed an increase as did normotensive subjects. Patients with decreased basal ACA after exercise also showed a lower ACA stimulation by IPR, F, Gpp (NH)p and Gpp(NH)p+IPR, which did not change after exercise. These patients also exhibited substantial rises in PRA with exercise. These was an inverse relationship between exercise-induced changes in PRA and basal ACA. So the acute regulation of lymphocyte BARD-ACA system is changed in a subset of patients with EH. The pattern of the regulation of this lymphocyte system is associated that of baseline renin activity and of its response to exercise in patients with EH.
...
PMID:[The effect of a submaximal physical load on the beta 2-adrenoreceptor-dependent adenylate cyclase system of the lymphocytes in hypertension]. 255 57

Since a significant heritability has been shown for forskolin stimulation of lymphocyte adenylate cyclase activity in twins, we evaluated lymphocyte forskolin-stimulated adenylate cyclase activity with respect to a familial predisposition towards essential hypertension. Lymphocyte adenylate cyclase activity was measured in broken cell preparations of 32 male normotensive volunteers with (n = 15) and without (n = 17) a positive family history of hypertension. The maximal forskolin stimulation of adenylate cyclase activity was significantly higher in the positive compared with the negative group (maximal stimulation of activity 53.5 +/- 3.4 versus 41.2 +/- 1.9 pmol cyclic AMP (cAMP)/mg protein per min; P less than 0.01). Dose-response curves showed a significantly greater stimulation of adenylate cyclase activity in the positive group at forskolin concentrations of 10(-7) to 2 x 10(-4) mol/l. The median effective dose (ED50) and adenylate cyclase activity in the absence of forskolin were similar in both groups. We conclude that lymphocyte forskolin-stimulated adenylate cyclase activity may depend in part on hereditary factors associated with a familial predisposition to essential hypertension.
...
PMID:Increased forskolin stimulation of lymphocyte-adenylate cyclase in normotensive subjects predisposed to essential hypertension. 263 96

As many as 118 middle-aged and elderly patients suffering from essential hypertension with different stages of circulatory failure (CF) were examined. In elderly patients suffering from CF, the activity of the renin-angiotensin-aldosterone system turned out lower while the adenylate cyclase system was activated earlier than in middle-aged patients. Introduction of verapamil into a complex of therapeutic measures promoted stabilization or reduction of aldosterone concentration in plasma, induced prolonged diuresis, and diminished acute losses of electrolytes. These circumstances formed the basis for combined use of digoxin, furosemide and verapamil in the treatment of elderly patients suffering from circulatory failure.
...
PMID:[The use of digoxin, lasix and finoptin in treating circulatory failure in hypertension]. 268 70


1 2 3 Next >>

---