Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme inhibitors are potent vasodilators acting by inhibition of production of the vasoconstrictor angiotensin II. In adults, they are used for treatment of systemic hypertension and congestive heart failure and investigated for treatment of primary pulmonary hypertension. In infants and children, saralasin and captopril were found to be useful in treatment of systemic arterial hypertension, especially when associated with high plasma renin activity. Captopril has failed in the treatment of congestive heart failure associated with complex congenital heart diseases and in most cases of primary pulmonary hypertension. It has a clear beneficial effect in coarctation of the aorta and may have such an effect in endomyocardial diseases and ventricular septal defect. In adults, serious side effects have limited the use of captopril. New converting enzyme inhibitors, devoid of a sulfhydryl group, are expected to have a better safety profile.
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PMID:Cardiovascular drugs in children: angiotensin-converting enzyme inhibitors. 304 87

The major antihypertensive mechanism of calcium antagonists is by decreasing the systemic vascular resistance, modified by the counter-regulatory responses of the baroreflexes and the renin-angiotensin-aldosterone system. In severe hypertension, the concept that calcium overload of the vascular myocyte could precipitate or aggravate peripheral vasoconstriction provides a logical basis for the use of these agents as first choice therapy; nifedipine, especially, has been well tested. As monotherapy for mild to moderate hypertension each of the three first-generation agents compares well with beta-blockers. Calcium antagonists may have a special role in the therapy of certain patient groups (elderly, black) or in those subjects whose life style involves intense physical or mental exertion (hemodynamics better maintained than with beta-blockade) or in patients with early end-organ damage such as left ventricular hypertrophy or renal insufficiency. However, the goal blood pressure may not be reached during monotherapy so that drug combinations may be required. Further indications for these compounds are as follows. Verapamil and diltiazem are frequently used in supraventricular tachycardias including acute and chronic atrial fibrillation. In the arrhythmias of the Wolff-Parkinson-White syndrome, there is the potential danger of provocation of anterograde conduction. Further indications for calcium antagonists, still under evaluation, include congestive heart failure (controversial), hypertrophic cardiomyopathy (verapamil), primary pulmonary hypertension (high doses required), Raynaud's phenomenon (nifedipine and diltiazem effective), peripheral vascular disease (proof not yet documented), cerebral insufficiency and subarachnoid hemorrhage (nimodipine promising), migraine, exertional bronchospasm, renal disease, atherosclerosis (experimental), and primary aldosteronism (nifedipine inhibits aldosterone release). Second-generation agents include dihydropyridines, such as nitrendipine, nicardipine, felodipine, amlodipine, nisoldipine, nimodipine, and isradipine. From these will be selected agents that are longer acting and provide higher vascular selectivity. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine. Yet caution is required when calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as alpha-adrenergic blockers, beta-adrenergic blockers, digoxin, quinidine, and disopyramide.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Calcium channel antagonists. Part III: Use and comparative efficacy in hypertension and supraventricular arrhythmias. Minor indications. 315 29

The blood pressures (BP) of the parents of a group of students were determined and two subgroups of students were defined, one with (PHT group) and one without (PNT group) a familial predisposition to hypertension. Observations were made in both groups during three periods of modified dietary electrolyte intake: (i) no-added sodium (low Na), (ii) no added sodium with potassium supplementation (low Na/high K), and (iii) sodium supplementation (high Na). The diets were given in random order. At the start of the trial, while the students continued their customary diet, the PHT group had higher systolic and diastolic pressures and plasma noradrenaline levels than the PNT group. At the end of 4 weeks of the high Na diet, the BP levels of both groups were significantly higher than those after the low Na diet. In contrast, when the low Na diet was supplemented for 2 weeks with potassium, BPs of the PHT group fell significantly, while those of the PNT group rose slightly. BP in the PHT group was significantly lower during the low Na/high K than during the high Na diet (systolic 10.5 mm Hg +/- 2.3 SE; diastolic 11.2 +/- 2.5, the changes being significantly different from those in the PNT group. The changes in plasma renin and aldosterone were similar in both groups during the different diets. Plasma noradrenaline fell in the PHT group, but rose in the PNT group when the low Na diet was supplemented with potassium. This fall in plasma noradrenaline in the PHT group during the low Na/high K diet correlated with the falls in systolic and diastolic BP. It is concluded that whereas young adults with a familial predisposition to hypertension behave similarly to those without such a predisposition in having a pressor response to a high sodium intake, they are peculiar in showing a depressor response to a high potassium intake.
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PMID:Blood pressure and hormonal changes following alteration in dietary sodium and potassium in young men with and without a familial predisposition to hypertension. 610 98

Prostacyclin (or epoprostenol), an arachidonic acid metabolite, is an effective treatment for patients with primary pulmonary hypertension. Interruption of chronic prostacyclin infusion can result in recurrent symptoms of dyspnea and fatigue. The etiology of this phenomenon is unknown. We hypothesized that sympathoadrenal activation could lead to increased vascular tone after abrupt termination of the infusion. To evaluate this effect, we monitored six chronically instrumented, awake sheep during and after infusion of prostacyclin. Prostacyclin decreased mean arterial pressure (MAP) by 14% and increased cardiac output by 33%. After the infusion ceased, MAP rebounded 23% above baseline, and cardiac output decreased by 28% from peak values within 10 min. We were unable to demonstrate an increase in norepinephrine levels after cessation of prostacyclin, nor did alpha-adrenergic blockade affect postinfusion hemodynamics. However, plasma renin activity increased >10-fold at peak infusion and remained elevated for up to 2 h after discontinuation of prostacyclin. Coinfusion of the angiotensin II-receptor antagonist L-158,809 resulted in complete abrogation of the postcessation rise in MAP. We conclude that renin-angiotensin system activation is primarily responsible for systemic hypertension occurring after abrupt cessation of prostacyclin infusion in sheep and that angiotensin II receptor blockade prevents this response. Our data do not support a role for sympathetic nervous system activation in the systemic pressor response after prostacyclin infusion.
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PMID:Angiotensin II mediates systemic rebound hypertension after cessation of prostacyclin infusion in sheep. 968 53

The present review is focused on chronic RV pressure overload or Cor Pulmonale as it may occur in the setting of two distinct disorders: those associated with abnormal pulmonary gas exchange (hypoxemia and/or hypercapnia) where chronic obstructive pulmonary disease (COPD) is the leading cause, and those associated with pulmonary vascular obstruction where primary pulmonary hypertension (PDDH) is the representative example. The clinical curse, prognostic, implications, and therapeutic strategies differ considerably in these two clinical entities. Right ventricular failure (RVF) may adversely influence the natural history and prognosis of patients with diverse cardiopulmonary disorders. It has been long established that right ventricular (RV) ischemia, RV overload, and RV pressure overload, alone or in combination, are the main factors involved in the pathogenesis of RVF. From the pathophysiologic point of view, RVF of COPD is more a congestive type of failure, in which activation of renin-angiotensin system is involved. In PPH, a low cardiac output state is predominant and the precise mechanism of RVF remains unknown. Current evidence in favor of the pathogenetic role of ischemia, adrenergic overdrive, and genetic determination are all reviewed during the course.
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PMID:[Right ventricle insufficiency in pulmonary arterial hypertension. Physiopathologic considerations]. 1156 26

Some studies suggest a higher risk of hypertension in people with epilepsy. Captopril, a potent and selective angiotensin-converting enzyme (ACE) inhibitor, is a well known antihypertensive drug. Besides the peripheral renin-angiotensin system (RAS), ACE inhibitors are also suggested to affect the brain RAS which might participate in the regulation of seizure susceptibility. The purpose of the current study was to evaluate the effect of captopril on the protective action of numerous antiepileptic drugs (carbamazepine [CBZ], phenytoin [PHT], valproate [VPA], phenobarbital [PB], oxcarbazepine [OXC], lamotrigine [LTG] and topiramate [TPM]) against maximal electroshock-induced seizures in mice. This study was accompanied by an evaluation of adverse effects of combined treatment with captopril and antiepileptic drugs in the passive avoidance task and chimney test. Captopril (25 and 50 mg/kg i.p.) did not influence the threshold for electroconvulsions. Among the tested antiepileptics, captopril (25 and 50 mg/kg i.p.) potentiated the antiseizure action of CBZ, decreasing its ED(50) value from 12.1 to 8.9 and 8.7 mg/kg, respectively. Moreover, captopril (50 mg/kg i.p.) enhanced the anticonvulsant activity of LTG. ED(50) value for LTG was lowered from 5.1 to 3.5 mg/kg. The observed interactions between captopril and CBZ or LTG were pharmacodynamic in nature as captopril did not alter plasma and total brain concentrations of these antiepileptics. The combinations of captopril with antiepileptic drugs did not lead to retention deficits in the passive avoidance task or motor impairment in the chimney test. Based on the current preclinical data, it is suggested that captopril may positively interact with CBZ and LTG in epileptic patients. The combinations of captopril with the remaining antiepileptics (PHT, VPA, PB, OXC and TPM) seem neutral.
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PMID:Captopril potentiates the anticonvulsant activity of carbamazepine and lamotrigine in the mouse maximal electroshock seizure model. 2071 8

Antenatal maternal hypoxia (AMH) can lead to intrauterine growth restriction (IUGR), as well as idiopathic pulmonary hypertension of newborn and adult, the latter of which may be a consequence of alterations in the local pulmonary renin-angiotensin system (RAS). Little is known of these adaptations, however. Thus, we tested the hypothesis that antenatal maternal hypoxia is associated with alterations in gene and protein expression of the pulmonary renin-angiotensin system, which may play an important role in pulmonary disorders in the offspring. In FVB/NJ mice, we studied messenger RNA (mRNA) and protein expression, as well as promoter DNA methylation and microRNA (miRNA) levels in response to 48 hours hypoxia (10.5% O(2)) at 15.5 day post coitum (DPC). In response to AMH, the pulmonary mRNA levels of angiotensin-converting enzyme (ACE) 1.2, ACE-2, and angiotensin II type 1b (AT-1b) receptors were increased significantly, as compared to controls (N = 4). In response to antenatal hypoxia, pulmonary protein levels of renin and ACE-2 also were increased significantly, whereas ACE-1 protein expression was reduced. In fetal lungs, we also observed reduced expression of the miRNAs: mmu-mir -199b, -27b, -200b, and -468 that putatively increase the translation of renin, ACE-1, ACE-2, and AT-1 receptors, respectively. In response to AMH, promoter methylation of ACE was unchanged. We conclude that AMH leads to changes in expression of pulmonary RAS of fetal mice. The possible implications of these changes for the regulation of pulmonary vascular contractility in later life remain to be explored.
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PMID:Antenatal maternal hypoxic stress: adaptations in fetal lung Renin-Angiotensin system. 2097 79