ABSTRACT
The roles of cGMP, prostaglandins, the entry of extracellular Ca2+ through slow channels, endothelium and V1 receptors in the negative inotropic, chronotropic and coronary vasoconstrictor responses to arginine vasopressin (AVP) have been investigated in isolated perfused rat hearts. The bolus injection of 5 x 10(-5) M AVP produced a significant decrease in contractile force, heart rate and coronary flow. AVP also significantly decreased contractile force, heart rate and coronary flow in hearts pretreated with an inhibitor of soluble guanylate cyclase methylene blue (10(-6) M), an effective drug for removing endothelium saponin (500 micrograms/ml), an inhibitor of cyclooxygenase indomethacin (10(-5) M) or a calcium channel antagonist verapamil (5 x 10(-7) M). The potent V1 receptor antagonist [Deamino-Pen1, Val4, D-Arg8]-vasopressin (9 x 10(-5) M) did not alter effects of AVP but the very potent V1 receptor antagonist [beta-Mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin (8 x 10(-5) M) abolished these effects. Our results suggest that AVP produces negative inotropic, chronotropic and coronary vasoconstrictor effects in isolated perfused rat hearts. cGMP, prostaglandin release and Ca2+ entry does not involve in the effects of AVP. These effects are endothelium independent and mediated by V1 receptors. The use of V1 receptor antagonist [beta-mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin may be beneficial for preventing the negative inotropy, chronotropy and coronary vasoconstriction induced by AVP.
Subject(s)
Coronary Circulation/drug effects , Heart Rate/drug effects , Heart/drug effects , Myocardial Contraction/drug effects , Vasoconstrictor Agents/pharmacology , Vasopressins/pharmacology , Animals , Coronary Circulation/physiology , Female , Heart/physiology , Heart Rate/physiology , Male , Myocardial Contraction/physiology , Rats , Rats, Wistar , Receptors, Vasopressin/drug effects , Receptors, Vasopressin/physiologySubject(s)
Hemorrhage/physiopathology , Ischemia/physiopathology , Kidney/physiopathology , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/physiology , Vasoactive Intestinal Peptide/pharmacology , Animals , Blood Transfusion , Hemorrhage/pathology , Histamine Release/drug effects , Ischemia/pathology , Kidney/drug effects , Kidney/pathology , Male , Malondialdehyde/metabolism , Mast Cells/drug effects , Mast Cells/pathology , Mast Cells/physiology , Necrosis , Rats , Rats, Sprague-DawleyABSTRACT
The role of nitric oxide (NO) in the regulation of coronary flow and mechanical function under basal conditions and when exposed to nifedipine was studied in perfused rat hearts. Inhibition of basal release of NO by bolus injections of NG-nitro-L-arginine (L-NNA) (90 mM) and NG-nitro-L-arginine methyl ester (L-NAME) (185, 370 and 740 mM) induced significant decrease in coronary flow, contractile force and heart rate. L-NAME in the doses of 185, 370 and 740 mM also decreased significantly contractile force and heart rate during treatment with 170 microM nifedipine. However, the same doses of L-NAME caused an insignificant reduction in coronary flow in the presence of nifedipine. These findings suggest that NO has an important role in the regulation of coronary flow and mechanical performance under basal conditions and during the hearts exposed to nifedipine. Nifedipine may attenuate the myocardial ischaemia induced by the loss of NO production.
