Late phase of nitroglycerin-induced coronary vasodilatation blunted by inhibition of prostaglandin synthesis.

Abstract

In chloralose-anesthetized dogs with the left circumflex coronary artery perfused at constant flow, the effects of increasing doses of indomethacin or naproxen on the coronary and systemic hemodynamic responses to a 5 gg intracoronary injection of nitroglycerin (NTG) were evaluated. The integrated areas of NTG-induced coronary vasodilatation were reduced after administration of indomethacin or naproxen. The extent of this reduction was increased progressively by augmenting the dose of indomethacin and naproxen up to 1.5 and 7 mg/kg, respectively. We also assessed the extent of cyclooxygenase inhibition induced by indomethacin or naproxen through the radioimmunoassay of thromboxane B2, which reflects thrombin-induced activation of platelet thromboxane A2 production during whole blood clotting. The level of inhibition progressively increased and complete inhibition was attained with 1.5 mg/kg indomethacin and 7 mg/kg naproxen. Further increase in dosage failed to induce further reduction of integrated areas of coronary vasodilatation, and a correlation was found between the extent of the reduction of the integrated areas of coronary vasodilatation and the dose of indomethacin (r = .828, n = 35, p < .001) or naproxen (r = .729, n = 35, p < .001). Finally, the NTG-induced maximum fall in coronary perfusion pressure remained unmodified after inhibition of prostaglandin synthesis, but there was a faster return of the perfusion pressure to the basal value. Furthermore, additional experiments performed with constant intracoronary infusion of NTG (60 gg/min for 4 min) showed that when a steady-state condition was reached, the pretreatment with indomethacin or naproxen also reduced the first part of the integrated areas of coronary vasodilatation (from the beginning to the end of the NTG infusion) (

Effect of Cyclooxygenase Blockade on the Beneficial Actions of Nicorandil in the Stunned Myocardium of Dogs

“…Since there have been several studies which have suggested a role for prostacyclin or other vasodilatory prostaglandins in the antianginal actions of nitrates including ni corandil [Neichi et al, 1980;Schor et al, 1981;Nakabayashi et al, 1985;Trimarco et al, 1985], the present study was designed to test the hypothesis that the beneficial actions of nicorandil in the stunned myocardium were at least partially the result of an in crease in vasodilatory prostaglandins or a decrease in TxA2. The results clearly indicate that this is not the case, since indomethacin, in doses which produced nearly a 100% inhi bition of cyclooxygenase, did not block the salutory actions of nicorandil.…”

Preferential venoconstriction by cyclooxygenase inhibition in vivo without attenuation of nitroglycerin venodilation.

“…Intervals of at least 2 weeks were allowed between two consecutive protocols in the same dog. The protocols [5][6][7] required acute laparatomy in anesthesia for place-ment of occlusive snares around arteries of the splanchnic bed or the hindquarter bed (Table 1). At the end of one of these protocols, the dogs were killed by an overdose of pentobarbital.…”

Gastric Arteriolar and Venular Responses to Nitrogenous and Nonnitrogenous Vasodilating Agents in the Rat

“…This mechanism may be responsible for the marked vasodilation induced by NTG and SNP. NTG, however, has also been shown to release prostaglan din (PGH) and subsequently stimulate the formation of cyclic AMP which also promotes vascular smooth muscle relaxation [26,27], The involvement of PGH has been reported to account for the persistence of reduction in cor onary resistance [28]. NTG-induced PGIi has been shown to contribute to the vasodilatory action of organic nitrates in the fetoplacental circulation [29].…”