dinoprost and Tachycardia

The roles of prostanoids in the pathogenesis of cardiovascular diseases and in the development of pathological conditions have been examined using mice lacking the individual, specific prostanoid receptor. Prostaglandin (PG) I2 protected the heart from ischemia-reperfusion injury in a model of acute myocardial infarction. In addition, PGI2 suppressed the development of pressure overload-induced cardiac hypertrophy. Aside from its potent vasodilatory action, PGI2 contributed critically to the development of renovascular hypertension via the activation of the renin-angiotensin-aldosterone system. Thromboxane (TX) A2 and PGF2alpha were found to be the mediators of inflammatory tachycardia under a systemic inflammatory condition induced by lipopolysaccharide. Under a septic condition leading to a vascular hypo-responsive state, TXA2 worked to maintain vascular tone by inhibiting the induction of inducible nitric oxide synthase in vascular smooth muscle cells. Mice lacking the PGE2 receptor subtype EP3 had a bleeding tendency and were resistant to thromboembolism, due to a defective activation of platelets. From these studies, the important and novel roles of prostanoids in the pathogenesis of cardiovascular diseases have been clarified.

Topics: Animals; Blood Platelets; Cardiomegaly; Cardiovascular Diseases; Dinoprost; Epoprostenol; Hemodynamics; Humans; Hypertension, Renovascular; Inflammation Mediators; Mice; Mice, Knockout; Myocardial Reperfusion Injury; Prostaglandins; Receptors, Prostaglandin; Sepsis; Signal Transduction; Tachycardia; Thromboxane A2

Since prostaglandin (PG) F2 alpha had been shown to act anti-arrhythmically in various animal models and also in preliminary investigations in man, further evaluation of this effect was made in 30 patients with cardiac extrasystoles and in 2 patients with tachycardias. PGF2 alpha was infused intravenously at individually adapted consecutive rates from 5 to 100 micrograms/min each for at least 5 min. In the incidence of extrasystoles a mean maximum decrease of 41% (P less than 0.001) was obtained. One patient showed repeated short interruptions of a ventricular tachycardia. A dose-dependent significant rise in blood pressure and no significant influences on heart rate, PQ interval and QRS interval of the ECG were found. It is concluded that PGF2 alpha has probably no practical importance for the therapy of cardiac arrhythmias.

Topics: Adult; Aged; Arrhythmias, Cardiac; Blood Pressure; Clinical Trials as Topic; Dinoprost; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Prostaglandins F; Tachycardia

Systemic inflammation induces various adaptive responses including tachycardia. Although inflammation-associated tachycardia has been thought to result from increased sympathetic discharge caused by inflammatory signals of the immune system, definitive proof has been lacking. Prostanoids, including prostaglandin (PG) D(2), PGE(2), PGF(2alpha), PGI(2) and thromboxane (TX) A(2), exert their actions through specific receptors: DP, EP (EP(1), EP(2), EP(3), EP(4)), FP, IP and TP, respectively. Here we have examined the roles of prostanoids in inflammatory tachycardia using mice that lack each of these receptors individually. The TXA(2) analog I-BOP and PGF(2alpha) each increased the beating rate of the isolated atrium of wild-type mice in vitro through interaction with TP and FP receptors, respectively. The cytokine-induced increase in beating rate was markedly inhibited in atria from mice lacking either TP or FP receptors. The tachycardia induced in wild-type mice by injection of lipopolysaccharide (LPS) was greatly attenuated in TP-deficient or FP-deficient mice and was completely absent in mice lacking both TP and FP. The beta-blocker propranolol did not block the LPS-induced increase in heart rate in wild-type animals. Our results show that inflammatory tachycardia is caused by a direct action on the heart of TXA(2) and PGF(2alpha) formed under systemic inflammatory conditions.

Topics: Animals; Blood Pressure; Dinoprost; Electrocardiography; Heart Atria; Heart Rate; Inflammation; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mice, Knockout; Propranolol; Receptors, Prostaglandin; Receptors, Thromboxane A2, Prostaglandin H2; Tachycardia; Thromboxane A2

Topics: Adult; Anesthesia; Cervix Uteri; Dinoprost; Female; Humans; Injections; Tachycardia

The effects of 15(S) 15-methyl-PGF2 alpha were studied on the cardiovascular system of dogs. Intravenous and intravertebral artery administration of 15(S)-methyl-PGF 2 alpha induced arterial hypertensive and respiratory effects more intense and longer lasting than those observed for PGF2 alpha. Intravenous administration of 15(S) 15-methyl-PGF2 alpha induced a decrease of vascular reactivity to 1-norepinephrine and 1-epinephrine and to carotidal occlusion. Infiltration of the carotid sinus walls with 15(S) 15-methyl-PGF2 alpha decreased the baroreceptor reactivity.

Topics: Animals; Blood Pressure; Bradycardia; Cardiovascular System; Carotid Sinus; Dinoprost; Dogs; Heart Rate; Hypertension; Injections, Intra-Arterial; Prostaglandins F; Respiration; Tachycardia; Venous Pressure; Vertebral Artery