Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments in inbred strains of normotensive and hypertensive rats have clearly demonstrated circadian rhythms in blood pressure and heart rate. Pre- and postsynaptic signal transduction processes in vitro can, but need not, vary with circadian time, greatly depending on the strain of rats investigated. These data highlight the notion of a strain-dependent, and thus genetic, regulation of the cardiovascular system. Obviously, circadian rhythms in blood pressure cannot be explained by single biochemical parameters, but results from both in vitro and in vivo studies give first evidence that the vascular nitric oxide-cGMP system may be involved in the circadian regulation of blood pressure in WKY and SHR rats. In secondary hypertensive TGR and in their normotensive controls, SPRD, the guanylyl cyclase system does not seem to play a role in circadian blood pressure regulation. In neither of the four strains studied did aortic adenylyl cyclase show any time-dependent variation. Because vascular tissue was taken from the thoracic aorta of the rats, a contribution of adenylyl cyclase to circadian blood pressure regulation in small resistance arteries cannot be ruled out. Further studies in different parts of the vascular tree are needed to definitely answer that question. No data are available on time-dependent variation in the activity of phospholipase C, the second messenger pathway of vascular alpha-adrenoceptors and angiotensin II AT1-receptors, both of which mediate vasoconstriction. Future research into this system will be helpful in identifying mechanisms involved in blood pressure regulation in SPRD and TGR.
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PMID:Signal transduction in animal models of normotension and hypertension. 885 34

Soluble guanylyl cyclase activity and its stimulation by diethylamineNONOate was measured in aortae from hypertensive TGR(mREN2)27 rats (TGR) and Sprague-Dawley controls. Superoxide dismutase was added in vitro to evaluate the contribution of oxidative breakdown of nitric oxide (NO) by superoxide anions. Expression of soluble guanylyl cyclase was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Basal and stimulated soluble guanylyl cyclase activity was significantly reduced in TGR rats, addition of superoxide dismutase had no effect. Expression of soluble guanylyl cyclase subunits was not different between strains. The independent contribution of hypertension and the overactive renin-angiotensin system to soluble guanylyl cyclase subsensitivity was assessed after normalization of TGR's blood pressure by the Ca(2+)-channel blocker amlodipine or the angiotensin converting enzyme-inhibitor enalapril. Soluble guanylyl cyclase activity in TGR was slightly increased by amlodipine and almost completely restored by enalapril. In conclusion, TGR showed desensitized vascular soluble guanylyl cyclase, depending on their overactive renin-angiotensin system.
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PMID:Contribution of the renin-angiotensin system to subsensitivity of soluble guanylyl cyclase in TGR(mREN2)27 rats. 1096 40

It is still a controversial issue whether different classes of antihypertensive drugs are equally effective in the regression of cardiac hypertrophy and associated complications. The present study compared the effects of prolonged treatment with the Ca2+-channel blocker amlodipine and the ACE inhibitor enalapril, respectively, in TGR(mREN2)27 rats (TGR), an animal model of renin-dependent hypertension. TGR were divided into three groups and received either amlodipine, enalapril or drinking water without addition, Sprague-Dawley rats (SPRD) served as normotensive control group. Cardiovascular parameters were monitored by radiotelemetry, and drug doses were titrated until 24-h blood pressure was reduced to approximately 140/90 mmHg in both active treatment groups. After 8 weeks of treatment left ventricular (LV) hypertrophy was completely reversed in both treatment groups despite a tenfold increase in plasma angiotensin II in amlodipine-treated TGR. In untreated TGR LV catecholamines were depleted, and beta1-adrenergic stimulation of adenylyl cyclase was blunted. Treatment of TGR with enalapril prevented both the depletion of tissue catecholamines and the desensitisation of LV beta1-adrenoceptors. Amlodipine had no effect on cardiac adrenergic signal transduction. Basal activity of LV soluble guanylyl cyclase was not different between TGR and SPRD, but its sensitivity to stimulation by nitric oxide was slightly reduced in TGR. Treatment had no effect on basal and stimulated guanylyl cyclase activity. The present study in an animal model of renin-dependent hypertension suggests that blood pressure reduction per se is sufficient for a regression of cardiac hypertrophy. However, beta-adrenergic desensitisation was prevented only in the enalapril-treated group, supporting a blood pressure-independent contribution of the renin-angiotensin system to the regulation of beta-adrenergic signal transduction.
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PMID:Normalisation of blood pressure in hypertensive TGR(mREN2)27 rats by amlodipine vs. enalapril: effects on cardiac hypertrophy and signal transduction pathways. 1119 27

In hypertensive TGR(mREN2)27 rats (TGR), the subsensitivity of vascular guanylyl cyclase to nitric oxide could depend on oxidized heme, reduced heme content, or decreased expression of the enzyme. In this study, enzyme activity was stimulated by protoporphyrin-IX, which acts independently of heme, and expression was assessed by Western blot analysis. In TGR aorta, maximum stimulation of soluble guanylyl cyclase by protoporphyrin-IX was 40% lower than in Sprague-Dawley controls, and expression of the beta1-subunit of the enzyme was reduced by 50% (P<0.05, t-test). In conclusion, decreased expression of soluble guanylyl cyclase leads to a blunted response of the nitric oxide-cGMP (guanosine 3',5'-cyclic monophosphate) pathway in TGR aorta.
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PMID:Mechanisms involved in the blunted nitric oxide-cGMP pathway in hypertensive TGR(mREN2)27 rats. 1124 48