Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cells are not just a semipermeable membrane that forms a barrier between the blood and the vascular smooth muscles. This cell system is a highly active metabolic endocrine organ. It not only produces a number of important substances in vascular and neural homeostasis but also inactivates vasoactive substances such as serotonin and bradykinin. In addition, it produces endothelin-1 and angiotensin II; more importantly in the context of migraine, endothelial cells produce the vasodilators prostacyclin and EDRF-NO, both of which are local (paracrine) hormones. The physiologic function of endothelial cells is affected by aspirin, which prevents prostacyclin formation but has little effect on normal blood pressure. From this information, one can infer that endothelial cell production of prostacyclin does not play an important part in normal cardiovascular control. On the other hand, the administration of Ng-monomethyl-L-arginine causes immediate increases in blood pressure. Because the administration of this substance inhibits the release of EDRF-NO, it appears that this paracrine endothelial hormone actively dilates the normal circulation. It is of cardinal importance that damage or flow perturbations of cell membranes of the endothelial lining of blood vessels cause an increased production of prostaglandins. However, smooth muscle cells underlying the endothelial lining also synthesize prostacyclin. This mechanism is thought to be held in reserve to reinforce local production of prostacyclin and vasodilatation when cell damage to the endothelial lining occurs and EDRF-No is not produced. Many theories for the causation of migraine have been proposed, and some have been reviewed. Those holding sway tend to ignore inconsistencies and cite supporting evidence in favor of their pet explanation only. I therefore have no hesitation to show that the best explanation at present, based on the most recent cellular evidence, explains all features of migraine and the response of migraineurs to therapy. The endothelial cell is the most likely site of the primary abnormality (Fig. 1). Although under physiologic circumstances perivascular innervation and endothelial systems closely interact in the control of vascular tone during pathologic conditions such as ischemia, the dominant role in protecting the circulation is endothelium-mediated. The biology of headache is so diverse and our ignorance sufficiently pervasive that the investigation of endothelial cell function may solve the mystery of migraine. To match the postulated crucial role of the endothelial cell in the pathogenesis of migraine, another cell would have to be ubiquitously present throughout the vasculature and not just confined to the central nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathogenesis of migraine. 202 Feb 28

Nitrates are old drugs, introduced into medical treatment more than 100 years ago, initially as a homeopathic remedy against headache (1850), and only later against angina pectoris (1867). Their typical hemodynamic, antiischemic effects were described in man in the 1950s and 1960s. They include: a reduction in venous return, lowering of the abnormally increased left ventricular enddiastolic pressure during ischemia, a decrease in left ventricular systolic wall stress, and changes in left ventricular geometry resulting in a decrease of myocardial oxygen consumption. The vasodilatory effect on large epicardial coronary arteries, especially on eccentric stenoses through relaxation of vascular smooth muscle tone was described even more recently (1980). This effect proved to be of considerable clinical importance both in angina at rest, that is during a primary increase in vasomotor tone (coronary artery spasm) as well as in angina provoked by exercise, where the increase in vasomotor tone and in the degree of stenosis is often due to a rise in alpha-sympathetic tone. The relaxing effect on the large coronary arteries is regarded as additive to the one on venous tone. The real clinical importance of nitrates became, however, evident only in the last decade with the discovery of EDRF, the so-called endothelial-derived relaxing factor, an endogenous compound of endothelial origin at least partly consisting of nitrous oxide and therefore, like nitrates, it exerts its effect through the stimulation of cGMP. The tendency for coronary arteries to constrict in presence of atherosclerosis is explained by the lack of EDRF, especially in the region of atherosclerotic plaques where the endothelium is often absent or has lost its endocrine function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The mechanism of action of nitrates, 1988 status]. 251 90

Within the last decade it became obvious that the treatment of angina pectoris alone is not sufficient. Modern goals include the optimization of anti-ischemic treatment ("silent myocardial ischemia") without compromising quality of life, as well as the reduction of fatal and non-fatal cardiac events. The failure of nitrates to continuously protect from myocardial ischemia ("nitrate tolerance") requires a modification of the current step-care recommendations for medical treatment. Numerous combinations of nitrates, betablockers and calcium channel blockers compensate for each other regarding their effects on heart rate, contractility, peripheral resistance and coronary blood flow. Recommendations for combination therapy decisively depend on the choice of the first-line drug. Only nitrates reduce myocardial preload by venodilation and substitute for EDRF-deficiency. After headaches disappear, nitrates do not affect quality of life and they are cheap. The nitrate-induced acceleration of heart rate should be compensated by the addition of beta-blockers or heart rate-decreasing calcium channel blockers. Therefore, the combination of nitrates with heart-rate-increasing calcium channel blockers, such as nifedipine, should be avoided. Many studies have proven the superiority of different double and triple therapies, as compared to their single components. A few reports, however, did not confirm this increase of anti-ischemic efficacy with combination therapy. The improvement of prognosis is proven for beta blockers without ISA in subgroups of patients with acute or post myocardial infarction and can be assumed for nitrates as well. With regard to prognosis, calcium channel blockers were inferior to nitrates and beta blockers. The combination of nitrates with a non-ISA betablocker should be preferred in post myocardial infarction patients with ventricular arrhythmias, whereas the combination of nitrates with a heart rate decreasing calcium channel blocker should be preferred in patients with COPD, severe peripheral arterial disease or severe diabetes. The combination of nitrates with a heart-rate-increasing calcium channel blocker should be considered in patients with sinus bradycardia, first degree AV-block, or proven coronary spasm. In patients with congestive heart failure, betablockers and calcium channel blockers should be avoided. To optimize medical treatment of ischemic heart disease, intermittent high dosage ISDN plus a beta blocker without ISA or ISDN plus a calcium channel blocker like verapamil are recommended. Frequently, however, the patient decides by himself, based on unacceptable side effects.
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PMID:[Combination of anti-angina drugs]. 257 81