Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Physiological roles have been suggested for prostacyclin in the cardiovascular system. Prostacyclin was administered by intravenous infusion to unanesthetized rats. Over a 24 hr period, 0.32 mg/kg/day caused only flushing of the ears. Larger doses (0.56 and 1 mg/kg/day) caused hypothermia, behavioral depression, and swelling of the paws. Cumulative dose-response curves for its depressor action were determined in both unanesthetized and anesthetized, vagotomized, ganglion-blocked rats. In unanesthetized rats, the threshold dose was about 0.1 ug/kg/min. Respiratory depression precluded doses larger than 1 ug/kg/min. In anesthetized rats, the threshold dose was about 0.001 ug/kg/min, and the maximally effective dose was about 0.1 micrograms/kg/min. At 0.032 ug/kg/min, blood pressure first fell and then rose slightly. This compensatory rise did not occur in nephrectomized rats, suggesting renin release as the mechanism. Intravenous infusion of 0.1 but not 0.01 ug/kg/min in unanesthetized rats doubled plasma renin activity. In saline-loaded unanesthetized rats, urine volume and urinary sodium excretion were decreased by 0.1 ug/kg/min of prostacyclin.
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PMID:The cardiovascular pharmacology of prostacyclin (PGI2) in the rat. 37 17

Prostacyclin (PGI2) is known to cause vasorelaxation and inhibit platelet aggregation by receptor-mediated mechanisms. While cyclic (c) AMP is known to act as a second messenger for inhibition of platelet aggregation, vasorelaxation by hyperpolarization has been described only recently and may provide an explanation, in addition to stimulation of cAMP for the PGI2 mechanism of action on blood vessels. When PGI2 is infused into healthy volunteers it reduces blood pressure only at infusion rates that also cause significant side-effects, primarily, nausea, emesis, flushing, diaphoresis, and restlessness. In hypertensive patients blood-pressure responses are complex and are influenced to some extent by renin secretion. PGI2 stimulates renin secretion by a direct effect on the juxtaglomerular apparatus, and it also has an indirect effect by activating the sympathetic nervous system. Thus, it is useless as an antihypertensive agent even apart from its debilitating side-effects. Vascular PGI2 is synthesized endogenously by both the endothelial cells and the muscularis of arteries. While the endothelial cells undoubtedly synthesize large amounts of PGI2, the muscularis comprises a much larger tissue mass so that the overall synthesis is about equally distributed between the endothelial and muscle cells. In patients with pregnancy-induced hypertension and some patients with essential hypertension endogenous synthesis of PGI2 has been evaluated by measuring 2,3-dinor-6-keto-PGF1 alpha and has proved to be greatly reduced. Some drugs (thiazides, propranolol) have been shown to stimulate PGI2 synthesis, and inhibition of cyclooxygenase has been shown to reduce their antihypertensive effects. The effects of low- and high-dose aspirin on prostacyclin and thromboxane synthesis are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Prostacyclin in hypertension]. 149 51

Co-dergocrine mesylate (Cod), which inhibits norepinephrine secretion by stimulating presynaptic dopamine receptors, and has no known metabolic side effect, has an additive antihypertensive effect to that of Nifedipine (Nif). Plasma norepinephrine, epinephrine, renin activity and aldosterone have been measured after acute administration of Nif and Cod alone and in combination to 18 patients with a diastolic blood pressure greater than 105 mmHg in a cross-over, randomized, double-blind study. Every patient received 4 mg Cod then 20 mg Nif, placebo then 20 mg Nif and 4 mg Cod then placebo. The second treatment was always given 1 h after the first medication. Blood pressure was measured before and every 15 min during the study period. Blood for measurement of catecholamines, aldosterone and renin activity was collected before medication, 1 h after the first dose and 90 min after the second treatment. Blood pressure was significantly lower (P less than 0.05) where Cod preceded Nif. Cod caused a significant decrease in plasma norepinephrine from 293 to 202 pg.ml-1 and in epinephrine from 67 to 55 pg.ml-1. The Nif-induced increase in norepinephrine from a pre-treatment value of 293 pg.ml-1 with preceding Cod to 331 pg.ml-1 was much less than the increase with placebo as premedication, from 284 to 440 pg.ml-1. Nif caused an increase in renin activity but no increase in aldosterone. Nif-related side effects, such as flushing and headache, occurred in 6 patients of whom 5 had no received Cod as premedication.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Co-dergocrine mesylate inhibits the increase in plasma catecholamines caused by nifedipine in essential hypertension. 207 34

Prostacyclin (PGI2) is known to cause vasorelaxation and inhibit platelet aggregation by receptor-mediated mechanisms. While cyclic (c)AMP is known to act as a second messenger for platelet aggregation, vasorelaxation by hyperpolarization has been described only recently and may provide an explanation, in addition to stimulation of cAMP, for the PGI2 mechanism of action on blood vessels. When PGI2 is infused into healthy volunteers it reduces blood pressure only at infusion rates that also cause significant side effects, primarily nausea, emesis, flushing, diphoresis and restlessness. In hypertensive patients blood pressure responses are complex and are influenced to some extent by secretion. PGI2 stimulates renin secretion by a direct effect on the juxtaglomerular apparatus, and also has an indirect effect by activating the sympathetic nervous system. Thus it is useless as an antihypertensive agent even apart from its debilitating side effects. Vascular PGI2 is synthesized endogenously by both the endothelial cells and the muscularis of arteries. While the endothelial cells undoubtedly synthesize larger amounts of PGI2, the muscularis comprises a much larger tissue mass so that the overall synthesis is about equally distributed between the endothelial and muscle cells. In patients with pregnancy-induced hypertension and some patients with essential hypertension, endogenous synthesis of PGI2 has been evaluated by measuring 2,3-dinor-6-keto-PGF1 alpha and has proved to be defective. Some drugs (cicletanine, thiazides, propranolol) have been shown to stimulate PGI2 synthesis, and inhibition of cyclooxygenase has been shown to abolish their antihypertensive effects. Whether stimulation of PGI2 synthesis affects the antihypertensive efficacy of these drugs is not yet known.
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PMID:Prostacyclin in hypertension. 225 88

The effects of nitrendipine and hydrochlorothiazide were studied in hypertensive elderly patients. Blood pressure was reduced (p less than 0.01) by both nitrendipine (13/10 +/- 4/3 mm Hg [n = 15], mean +/- SE) and hydrochlorothiazide (25/11 +/- 4/2 mm Hg [n = 16]). After hydrochlorothiazide, plasma glucose, uric acid, and renin activity increased and plasma potassium levels decreased. Edema and flushing were the main adverse reactions during nitrendipine. The response of blood pressure and heart rate to head-up tilt were not significantly different under both treatments. However, the effects of both drugs on diastolic blood pressure and norepinephrine responses to head-up tilt differed significantly. We conclude that, in the elderly, hydrochlorothiazide lowers systolic blood pressure more effectively than nitrendipine. However, nitrendipine does not have any of the potentially harmful metabolic side effects that were found during hydrochlorothiazide therapy. The clinical significance of a lower vasoreactivity during nitrendipine, as was found with the head-up tilt test, has to be established.
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PMID:Nitrendipine versus hydrochlorothiazide in hypertensive patients over 70 years of age. 292 May 3

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 mechanisms of the cardiovascular and renin responses to vasoactive intestinal polypeptide (VIP) are unclear. Rabbit studies suggest that VIP-induced tachycardia is largely beta-adrenoceptor mediated, but that the renin response may be partially prostaglandin-dependent. To examine the relative importance of prostaglandins and reflex sympathetic activation in the haemodynamic and renin responses to VIP infusion in man, we completed two randomised single-blind crossover studies in two groups of six healthy male volunteers (aged 24-35 years). We recorded the effects of indomethacin and propranolol pretreatment on VIP-related changes in heart rate (HR), blood pressure (BP), forearm vascular resistance (FVR), plasma renin activity (PRA), plasma noradrenaline (PNA) and plasma arginine vasopressin (AVP) concentrations. Intravenous VIP (calculated dose: 6 pmol kg-1 min-1) produced cutaneous flushing, increased HR and PRA, decreased FVR, but did not alter mean arterial BP or AVP levels. Indomethacin (375 mg over 3 days) lowered basal PRA and propranolol (circa 40 mg i.v. over 60 min) decreased resting HR and increased FVR. Although indomethacin and propranolol reduced the absolute rise in PRA and HR, respectively, during VIP infusion, the percentage changes were no different from control. Neither drug altered the flush response to VIP and propranolol did not affect the fall in FVR. We conclude that the measured cardiovascular responses to VIP infusion in man are probably direct and do not involve a significant contribution from reflex sympathetic stimulation, nor prostaglandin release.
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PMID:Effects of indomethacin and (+/-)-propranolol on the cardiovascular and renin responses to vasoactive intestinal polypeptide (VIP) infusion in man. 329 24

Hormonal and cardiovascular responses to 1-desamino-8-D-arginine vasopressin (DDAVP) were investigated in six normal adult volunteers. After overnight fluid deprivation, an intravenous injection of either DDAVP (0.4 microgram/kg) or the same volume of normal saline was administered. One hour later an intravenous infusion of hypertonic saline was commenced and continued over two hours. Five minutes following the DDAVP injection, facial flushing, a fall in diastolic blood pressure by an average of 13% and a rise in pulse rate by an average of 18% were observed. There was a significant increase in plasma renin activity and plasma cortisol concentration, but no significant changes were observed in plasma concentrations of LH, FSH, TSH, prolactin or GH. Following osmotic stimulation by hypertonic saline plasma AVP rose to the same extent in both the DDAVP and control studies. DDAVP (0.4 microgram/kg) was also administered to five subjects with cranial diabetes insipidus. Again facial flushing, increased facial temperature, a fall in diastolic pressure and a rise in heart rate were all observed, suggesting that DDAVP exerts its cardiovascular actions by a mechanism other than antagonism of circulating endogenous AVP.
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PMID:Hormonal and cardiovascular responses to DDAVP in man. 351 5

In man, intravenous infusion of adenosine has been useful in inducing sustained hypotension during anesthesia. Bolus injections terminate supraventricular tachyarrhythmias by delaying AV node conduction. It has been proposed that some of its cardiovascular effects are related to inhibition of noradrenergic neurotransmission. We assessed the cardiovascular and sympathoadrenal effects of intravenous infusion of adenosine (10 to 140 micrograms/kg/min) in 7 conscious normal subjects. At the highest infusion rate achieved, adenosine increased heart rate by 33 bpm (p less than 0.005), increased systolic blood pressure by 13 mm Hg (p less than 0.02) and decreased diastolic blood pressure by 8 mm Hg (p less than 0.02). Plasma norepinephrine and epinephrine increased 44% and 213% respectively. Basal plasma renin activity was 0.7 +/- 0.09 ng AI/ml/hr and remained unchanged. Higher doses were not given due to the appearance of subjective side effects (headache, nervousness, flushing and an urge to breathe deeply). During dipyridamole administration, 4-fold lower doses were required to produce equivalent cardiovascular effects. We conclude that in conscious man, intravenous infusion of adenosine is associated with activation rather than inhibition of the sympathoadrenal system. The possible mechanisms of this sympathetic activation are discussed.
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PMID:Cardiovascular effects of adenosine infusion in man and their modulation by dipyridamole. 353 3

The acute effects of a single, 20 mg oral dose of nitrendipine were studied in 10 women at between 32 and 42 weeks gestation with stable pregnancy-induced hypertension (PIH). Blood pressure (BP), maternal heart rate and fetal heart rate (FHR) were assessed for 8 h after nitrendipine intake together with the plasma levels of nitrendipine, noradrenaline, adrenaline, plasma renin activity (PRA) and vasopressin. The mean initial systolic/diastolic BP was 158 (SEM 3.7)/108 (SEM 2.7) mmHg. Within 1 h stable, reduced mean BP-levels of 141-145/90-95 mmHg were reached and maintained for 4 h after medication. This antihypertensive effect was closely related to the maternal plasma concentration of nitrendipine, which reached a maximum of 9.1 (SEM 2.6) ng/ml 3 h after tablet intake. After 4 h, systolic and diastolic BPs slowly increased in parallel to a successive decrease in plasma concentrations of nitrendipine. Maternal heart rate increased by less than 10%, while FHR remained unchanged. No hypotensive incidents occurred. The initial mean plasma concentrations of noradrenaline, adrenaline, vasopressin and PRA did not change during the treatment. No major maternal and no fetal side-effects were observed. Three of 10 patients experienced mild, transient facial flushing.
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PMID:Acute effects of nitrendipine in pregnancy-induced hypertension. 356 18


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