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)

Endogenous opioids are known to be involved in the pathophysiology of idiopathic headache. In fact, decreased levels of enkephalin (E) or endorphin (BE) during headache attacks might be a marker of an altered pain-inhibiting system of central neurotransmission or could be secondary to alterations of brain circulation that often occur during the headache crisis. Recently, captopril (C) has been shown to be apt to restore the availability of endogenous opioids, to improve cerebral blood flow via the inhibition of both the cerebral and systemic renin-angiotensin system or of catecholamine release. It has also been reported to be able to restore the nociceptive-antinociceptive balance through an increase of serum kinin (K) or prostaglandin (Pr) levels. In the present study, the efficacy of C in reducing the frequency (F), duration (D), or severity (S) of headache paroxysm were investigated in a double blind trial vs. placebo (P). Twenty-six subjects (5 males and 21 females; mean age 37 +/- 11 years) suffering from idiopathic headache at least for one year have been allocated to treatment with C (25 mg three times/day) or P according to a double-blind randomized protocol for 4 months. The effects of C or P have been evaluated with Migraine Index Correct, related to changes in F, D or S of headache attacks. Our results indicate that C is effective in reducing F, D or S in subjects with idiopathic headache.
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PMID:[Captopril versus placebo in the prevention of hemicrania without aura. A randomized double-blind study]. 149 69

Autoregulation of blood flow denotes the intrinsic ability of an organ or a vascular bed to maintain a constant perfusion in the face of blood pressure changes. Alternatively, autoregulation can be defined in terms of vascular resistance changes or simply arteriolar caliber changes as blood pressure or perfusion pressure varies. While known in almost any vascular bed, autoregulation and its disturbance by disease has attracted particular attention in the cerebrovascular field. The basic mechanism of autoregulation of cerebral blood flow (CBF) is controversial. Most likely, the autoregulatory vessel caliber changes are mediated by an interplay between myogenic and metabolic mechanisms. Influence of perivascular nerves and most recently the vascular endothelium has also been the subject of intense investigation. CBF autoregulation typically operates between mean blood pressures of the order of 60 and 150 mm Hg. These limits are not entirely fixed but can be modulated by sympathetic nervous activity, the vascular renin-angiotensin system, and any factor (notably changes in arterial carbon dioxide tension) that decreases or increases CBF. Disease states of the brain may impair or abolish CBF autoregulation. Thus, autoregulation is lost in severe head injury or acute ischemic stroke, leaving surviving brain tissue unprotected against the potentially harmful effect of blood pressure changes. Likewise, autoregulation may be lost in the surroundings of a space-occupying brain lesion, be it a tumor or a hematoma. In many such disease states, autoregulation may be regained by hyperventilatory hypocapnia. Autoregulation may also be impaired in neonatal brain asphyxia and infections of the central nervous system, but appears to be intact in spreading depression and migraine, despite impairment of chemical and metabolic control of CBF. In chronic hypertension, the limits of autoregulation are shifted toward high blood pressure. Acute hypertensive encephalopathy, on the other hand, is thought to be due to autoregulatory failure at very high pressure. In long-term diabetes mellitus there may be chronic impairment of CBF autoregulation, probably due to diabetic microangiopathy.
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PMID:Cerebral autoregulation. 220 48

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

Oxprenolol is a nonselective beta-adrenergic blocking agent that also possesses intrinsic sympathomimetic activity (ISA) and membrane stabilizing effects. Oxprenolol undergoes first pass metabolism with only 30% of an oral dose reaching the systemic circulation. The drug is approximately 80% protein bound and is eliminated primarily by glucuronidation in the liver. Less than 4% of oxprenolol is excreted unchanged in the urine. Oxprenolol may reduce the heart rate and prolong the effective and functional atrioventricular nodal refractory period. Oxprenolol has less negative inotropic and chronotropic effects than propranolol. Plasma renin activity is reduced; however, changes in plasma aldosterone level are not significant. Long term metabolic effects require further study. Oxprenolol appears to be comparable to other beta blockers in the treatment of hypertension and angina pectoris with no additional adverse reactions. If its partial agonist effect proves useful, it may have an advantage over other agents in treating patients with borderline cardiac reserve. Because of limited data, the use of oxprenolol for the treatment of arrhythmias, migraine, thyrotoxicosis, anxiety, and glaucoma cannot be recommended at this time.
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PMID:Oxprenolol hydrochloride: pharmacology, pharmacokinetics, adverse effects and clinical efficacy. 634 36

Calcitonin gene-related peptide (CGRP), a 37 amino acid peptide resulting from the specific maturation processes of calcitonin gene products, was discovered in 1982. Its messenger RNA was isolated from a calcitonin cancer in rats similar to the human thyroid medullary carcinoma. CGRP is closely related to calcitonin and amylin, and to a lesser extent, to the region coding for the alpha chains of relaxins, insulin and insulin growth factors. In thyroid C cells, calcitonin itself is the major gene product, but CGRP is predominant in the central and peripheral nervous system. CGRP is found in most all tissues and is considered to be a neuromediator of particular importance in the cardiovascular system. CGRP is a powerful endogenous vasodilator in man; plasma concentrations of 56 pmol/l (slightly above physiological levels) provoke flush, hypotension and secondary catecholamine release and subsequent tachycardia. Intravenous injections lead to systemic vasodilatation and redistribution of blood flow to the skin, the brain, and probably the splanchnic territory. It has been suggested that CGRP plays a role in blood pressure modulation in certain pathological conditions. CGRP level is decreased in hypertension and increased in septic shock. In patients with terminal renal failure, CGRP is correlated with excess volaemia. It could affect blood pressure by redistributing blood flow, interacting with the renin-angiotensin system or by inhibiting aldosterone secretion. CGRP may also play a role in modulating cutaneous vascular constriction in Raynaud's syndrome and cerebral vascularization in patients with migraine or meningeal hemorrhage subsequent to rupture of cerebral aneurisms. CGRP increases arterial flow in the cavernous body. Coronarian vascular tone and cardiac performance (positive chronotrope and inotrope effects) are improved. CGRP has also been studied in connection with glucose metabolism and may have other endocrine effects. Finally, CGRP increases electrolyte and water flow in the colon and its bronchoconstrictor effect could be implicated in asthma. The clinical significance of plasma CGRP is not yet known although it may be a marker of poor prognosis in thyroid medullary cancer. Recent studies suggest that CGRP could be a useful therapeutic agent in severe Raynaud syndrome, impotency, ischaemic neurological lesions due to ruptured aneurisms and in severe heart failure.
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PMID:[Calcitonin gene-related peptide (CGRP)]. 817 60

Because of the diversity of medical and social circumstances of women over 40, there are no general rules regarding contraceptive choices for them. Gynecological or general pathological conditions should be considered in selecting a method, as should harmful health habits such as alcoholism and smoking, and the habitual use of medications. Hormonal contraceptives are very effective and practical, and give indirect benefits such as regularization of the cycle and amelioration of brease disorder and dysmenorrhea, but they increase cardiovascular risks. The risk of death from myocardial infarct is multiplied by a factor of 34 for women over 40 who smoke. Pill use is associated with a modification of the serum lipids and a tendency to hypercoagulability and increased risk of thrombosis, as well as a deterioration of glucose tolerance and an increase of insulin secretion. The estrogen and progestin combined oral contraceptives (OCs) have opposing effects on lipid metabolism; the overall effect depends on the dosage, the compounds used, and the hormonal profile of the pill. Combined OCs cause an elevation of blood pressure that may appear immediately or progressively over time. Synthetic estrogens increase activity of the renin-angiotensin system, resulting in increased aldosterone levels, reduction of renal blood flow, and sodium retention. Smoking considerably increases vascular risk and is a contraindication to pill use after 35 years. In the absense of further study, it appears that OCs do not in general increase the risk of breast, endometrial, cervical, or ovarian cancer, and in some cases they reduce risk. Some physicians refuse to prescribe OCs to any patient over 40, but many others take a more flexible attitude. Absolute contraindications of OC use must be respected, and relative contrainidications suck as smoking, prediabetic status, and migraines become absolute for women over 40. Biphasic minipills may be the best choice because they combine effectiveness, small dose, and an equilibrated hormonal climate. Women over 40 who are multiparous, who desire no more children, who have no genital anomalies, and who have a stable conjugal life may be ideal candidates for IUDs. IUDs are effective and avoid many shortcomings of OCs. Their complications of perforation, ectopic pregnancy, and infection are infrequent and their possible impact on fecundity is less important in this group. Bleeding and pain are the main disadvantages, but pregesterone-releasing IUDs may reduce the volume of bleeding, combat endometrial hyperplasia and alleviate menstrual pain. Vaginal methods offer safe contraception to women for who other methods are contraindicated. Their effectivenes is less than that of pills or IUDs but still sufficient. Although sterilization is not legal in France except for some precise therapeutic in dications, it is a logical choice for premenopausal women in good health who have the desired number of children and a stable emotional life.
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PMID:[Contraception for women over 40]. 1226 11

Migraine is a common episodic headache that predominantly affects young adults, particularly women in their most productive years. Many of the prophylactic agents available today have side-effects that are not compatible with long-term use. The discovery that drugs influencing the renin-angiotensin system (RAS), which have few side-effects, were effective in some patients with migraine led to several studies investigating a possible link between the angiotensin system and migraine pathophysiology. Clinical trials indicated that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are effective in the prophylactic treatment of migraine. These findings are further supported by pharmacoepidemiological, genetic, and physiological studies. In addition, it is known that the RAS has neurophysiological, chemical, and immunological effects that are of relevance in migraine pathophysiology. On the basis of evidence presented in this review, we find it likely that the RAS has a clinically important role in migraine pathophysiology. The effect of ARBs and ACEIs on migraine is probably not attributable to their effect on blood pressure. The RAS has several actions that may be relevant in migraine pathophysiology, but the reason for the prophylactic effect of ARBs/ACEIs in migraine remains a matter of speculation.
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PMID:Involvement of the renin-angiotensin system in migraine. 1968 9

A new hypothesis is presented on the function of factor XII, which is postulated to be a "missing link" between acute stress and transient hypercoagulability. The implications of this idea are developed to show how chronic stress, which involves activation of hypertension and migraine as well as hypercoagulability, can cause of cerebrovascular disease. "Acute stress" is defined as "the normal short-term physiological response to the perception of major threats or demands". "Chronic stress" is "the abnormal ongoing physiological response to the continuing perception of unresolvable major threats or demands". The factor XII hypothesis is as follows: Acute stress includes release of epinephrine by the adrenal medulla. Epinephrine activates platelets by binding to alpha-2A adrenergic receptors. Activated platelets convert pre-bound factor XII to its active form, which then initiates the intrinsic coagulation cascade. This can be called the "activated platelet initiation pathway" for coagulation. Neither tissue factor nor pre-formed thrombin is required. Thrombosis proceeds to completion, but only a minute amount of thrombin is formed, and the process normally stops at this point. In people who lapse into a state of chronic stress, essential hypertension, which is also a manifestation of stress, synergizes with hypercoagulability: there is both a baseline rise in blood pressure and systemic platelet activation as well as superimposed labile rises of both. Upregulation of these two stress parameters is atherogenic: epinephrine-activated platelets stimulating thrombin formation interact with endothelial cells activated by angiotensin II to cause, first, smooth muscle cell proliferation, which is a histological hallmark of atherosclerosis, and, lastly, a symptomatic thrombotic occlusion-the stroke. The migraine symptoms which often accompany this process are a marker of chronic stress and ongoing pathophysiologic damage. Therapeutic predictions are made regarding novel ways of blocking stress-induced hypercoagulability and hypertension. Hypercoagulability could be targeted by monoclonal antibodies directed against the platelet-specific alpha-2 adrenergic receptor or the (putative) platelet receptor for Factor XII; hypertension could be treated with monoclonal antibodies directed against the beta-adrenergic receptor in the juxtaglomerular apparatus or by surgical denervation of the kidneys, either of which would decrease the renin release which helps drive the hypertension.
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PMID:Factor XII (Hageman factor) is a missing link between stress and hypercoagulability and plays an important role in the pathophysiology of ischemic stroke. 1675 26

Although the possibility of a comorbidity between migraine and hypertension has long been suspected, the epidemiologic evidence is controversial, with studies demonstrating positive, negative or no correlation between the two diseases. A unifying view that takes into account the most recent evidence suggests that there might be a different effect of diastolic and systolic pressure, with the former having a positive and the latter a negative correlation with migraine. In this paper, the methodologic and clinical reasons for the discrepancies in epidemiologic studies are discussed, together with the possible biological mechanisms that might account for the migraine-hypertension correlation. One such mechanisms may be the renin angiotensin system, which is certainly involved in hypertension and has activities in the CNS that may be relevant for migraine pathogenesis. Despite the uncertainty still present in this field, the control of hypertension in migraine patients is an important factor for the success of migraine treatment and to lower cerebrovascular risk.
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PMID:Migraine and hypertension. 1854 93

Several conditions are comorbid with migraine; our review is focused on the relation between migraine, and cerebrovascular and cardiovascular diseases. Despite many studies showed an association between migraine and patent foramen ovale, it is still not known whether its presence might be causal for the migraine pathogenesis and currently its closure cannot be recommended for migraine prevention. On the contrary, conflicting epidemiological data link migraine to arterial hypertension and the use of antihypertensive agents acting on the renin-angiotensin system sounds promising in migraine prevention. A complex bidirectional relation exists between migraine and stroke, and new evidences show a clear association between migraine and coronary heart disease. In both conditions, migraine represents a defined risk factor although the magnitude of the risk varies across the different studies. However, since the risk is low in the general population, it is not possible to identify which migraineurs will develop a cardiovascular or a cerebrovascular event making difficult to apply preventive measures.
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PMID:Comorbid neuropathologies in migraine: an update on cerebrovascular and cardiovascular aspects. 1860 Mar


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