| dc.description.abstract | The effect of PG32, PGF2a- and PGI2, on vasoconstriction induced by different mechanisms was studied in the isolated rat mesenteric artery as described by McGregor (1965). Vasoconstriction was induced by mechanisms involving different modes of calcium utilisation vis: (i) Pharmacomechanical pathway by low doses of the adrenergic neurotransmitter, noradrenalin acting at ά-receptor; (ii) electromechanical pathway by high potassium and (iii) agents which facilitate Ca2t influx e.g. A23187. The prostaglandins potentiated the vasoconstrictor effect of NA. Potentiation factors calculated free different doses of the prostaglandins showed the effects of the prostaglandins to be dose - dependent and PGE2 to be significantly core potent (p>0.005) than PGF2a- and PGI2. The prostaglandins failed to potentiate high potassium - induced vasoconstriction. PGE2 also failed to potentiate NA if the vasoconstrictor effects were evoked in Ca 2+ free Krebs solution; but the degree of potentiation increased with increase in the concentration of Ca 2+ ions in the perfusion fluid. This result suggested strongly that the potentiation was associated with external calcium. Evidence is presented to show that potentiation was not projunctional since cocaine, bretylium and reserpine pretreatment did not materially alter the effect of PGE2. It was concluded that prostaglandins potentiated NA vasoconstriction by facilitating Ca 2+ influx. The mechanism of this facilitation is discussed. NA vasoconstriction was competitively antagonised by adrenoceptor antagonists-phentolamine, tolazoline, yohimbine and phenoxybensamine (in low concentrations). The blockade caused by those antagonists was reversed by PGE2. By comparing NA dose-ratios in the presence of antagonist with dose-ratios in the presence of antagonists plus different doses of PGE2, I showed that the degree of reversal was related to the dose of PGE. For example, the NA dose - ratio for yohimbine (1.28 x 10-6M) was reduced from 26.6+0.9 to 1.7 + 0.1 when PGE2 (2.8 x 10-8M) was included in the perfusion fluid with the antagonist. The reversed of antagonist was not due to a change in the binding characteristics of the ά-adrenoceptor since PA2 values for the antagonist were not significantly different (P<0.05) when PGE was included with the antagonists. Evidence is presented which suggests that reversal of antagonism involved utilisation of internally bound calcium since reversal of antagonist occurred even after the omission of Ca 2+ from the external medium. In this sense, the mechanism of reversal was different from that of potentiation. Furthermore, the degree of reversal (measured as reversal factor) was quantitatively greater than would be case if reversal was simply a reflection of the enhanced responsiveness of the vascular muscle to NA.
In contrast to the “competitive” α-adrenoceptor antagonists, PGE2 did not reverse the block of NA vasoconstriction caused by phenoxybensamine (high doses); verapamil, cinnarizine or prazosin. All these agents caused blockade of NA that was not competitive in nature. Since none of the competitive α- adrenoceptor antagonists prevent prostaglandin formation; the point is made that a prostaglandin can reverse NA blockade even if the blockade did not involve inhibition of prostaglandin synthesis. | en_US |
