Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The actions of Platelet-Activating Factor (PAF) on isolated rat hearts were investigated. In a dose-dependent manner PAF decreased peak systolic pressure and maximum rate of rise of intraventricular pressure (+dP/dt(max]. PAF dose-dependently decreased coronary flow, prolonged the P-R interval of the EKG, and decreased heart rate. These actions of PAF were only partially blocked by drugs blocking receptors for PAF (CV 3988, WEB 2086), thromboxanes (ONO 3708), or leukotrienes (FPL 55712, L-655,240) or by a blocker of eicosanoid production (ibuprofen). Since depressed contractions will of themselves reduce coronary flow, PAF's action on flow was also investigated in hearts whose contractions were blocked by elevated potassium concentrations plus tetrodotoxin. Such treatment did not prevent PAF reducing coronary flow, indicating that a direct vasoconstriction occurred. The reductions in coronary flow in non-contracting hearts induced by PAF were equal to those induced by the coronary vasoconstrictors vasopressin and ergonovine under the same conditions. In order to isolate direct effects of PAF on myocardial contractile cells from effects mediated via changes in coronary flow, PAF was given to hearts maximally dilated by a concentration of nifedipine (0.03 microM) which had no effect on contractility. This concentration of nifedipine increased flow from 15.5 +/- 1.4 mL/min to 18.1 +/- 2.4 mL/min. In the presence of this nifedipine-induced vasodilation, PAF still exhibited negative inotropic actions, but without reducing coronary flow. Thus the effects of PAF on isolated rat hearts involve direct actions on both myocardial contracting cells and on coronary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Actions of platelet-activating factor on isolated rat hearts. 166 43

Anesthetized open-chest dogs were instrumented for the measurement of left circumflex coronary artery (LCX) blood flow and aortic blood flow, systemic arterial blood pressure, heart rate, lead II ECG, left ventricular end-diastolic pressure, left ventricular developed pressure and left ventricular positive and negative dP/dt to study the hemodynamic effects of leukotriene D4 (LTD4) and selective LTD4 antagonists on the coronary vasculature. Administration of LTD4 alone into the LCX (0.625-10 micrograms) produced a dose-dependent decrease in LCX blood flow, dP/dt and aortic blood flow and an increase in left ventricular end-diastolic pressure. Systemic arterial blood pressure, left ventricular developed pressure and heart rate were unchanged by LTD4. During i.v. infusions of the LTD4 antagonists, SK&F 102922 or FPL 55712 (1 mg/kg/min), the dose-dependent decreases in LCX flow, dP/dt and aortic blood flow were blocked whereas the increase in left ventricular end-diastolic pressure remained unchanged. The thromboxane A2 antagonist, SK&F 88046 (5 mg/kg + 0.1 mg/kg/min), which has been reported previously to block the coronary blood flow reducing action of LTC4, had no effect on the LCX blood flow responses to intracoronary LTD4. In a separate study, dogs instrumented in a similar manner were given bolus injections of arginine-vasopressin (1 microgram), the thromboxane A2 mimetic, U-46619 (10 micrograms), LTD4 (10 micrograms), angiotensin II (1 microgram) and prostaglandin F2 alpha (100 micrograms) directly into the LCX to provoke coronary vasoconstriction. SK&F 102922 and FPL 55712 selectively blocked the coronary vasoconstriction produced by LTD4, but had no effect on vasoconstriction produced by the other agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inhibition of leukotriene D4-induced coronary vasoconstriction by leukotriene antagonists in the anesthetized dog. 243 87

In anaesthetized beagles, saralasin, phentolamine, 1-penicillamine-2-O-methyl-tyrosine-8-arginine-vasopressin and SCH 23390, a DA1 antagonist, were infused into the left renal artery (i.r.a.) and indomethacin and aprotinin intravenously (Group 1). In Groups 2 and 3, i.r.a. infusion of two chemically different putative leukotriene (LT) antagonists, FPL 55712 (100 micrograms/kg/min) and LY 171883 (500 micrograms/kg/min), respectively, was superimposed in the fourth period of experiments. In comparison to Group 1, there was an increase (40% in Group 2 and 33% in Group 3) in renal blood flow and a decrease in glomerular filtration rate (16% and 17%, respectively) and filtration fraction (36% and 41%, respectively). Similar changes were observed on the single nephron level. Directly measured glomerular capillary pressure decreased by 10% and 12%, respectively. A decrease in total arteriolar resistance by 34% and 25%, respectively, was caused by a comparatively higher decrease in efferent (44% and 34%, respectively) than afferent (26% and 15%, respectively) arteriolar resistance values. No change in the ultrafiltration coefficient, Kf, was detected. Providing FPL 55712 and LY 171883 are specific LT antagonists, these experiments suggest a possible constrictory role of LT (expressed more on the efferent than afferent arteriole) in anaesthetised mildly surgically stressed dogs.
 ...
PMID:A possible role for leukotrienes in the regulation of glomerular haemodynamics in the dog. 284 54

The objective of this study was to determine whether arachidonate metabolites are involved in the vasoconstrictive effects of angiotensin II in rats. In the isolated perfused heart, dexamethasone (4 mg/kg) significantly suppressed the maximal decreases in coronary flow induced by angiotensin II and vasopressin (reference drug). In the heart, the nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1 muM) markedly suppressed the angiotensin II-induced decreases in coronary flow. NDGA (10 muM) inhibited both angiotensin II- and methoxamine- (reference drug) induced contractions in aortic rings with (in the presence of L-NAME) and without endothelium. In the heart, the leukotriene synthesis inhibitor MK-886 (0.3 muM) significantly reduced the maximal effects to angiotensin II, but the leukotriene antagonist FPL 55712 (0.1 and 0.3 muM) had no effect. We conclude that in the isolated perfused rat heart angiotensin II-induced decreases in coronary flow are in part mediated by Hpoxygenase products, which might be derived from the 5-Hpoxygenase pathway, but are probably not leukotrienes. Furthermore, endothelium independent Hpoxygenase products mediate part of the contractile responses to angiotensin II in the isolated rat aorta.
 ...
PMID:Role of lipoxygenase products in the effects of angiotensin II in the isolated aorta and perfused heart of the rat. 1847 74