Interaction Of Prostaglandin E (Pge ) With Noradrenaline And Its Antagonists In The Isolated Mesenteric Artery Oe Rat

ABSTRACT

The effect of PGE^, P5P?a and PGI0 on tilu lion induced by different mechanisms was studied in the isolated rat mesenteric arteiy as described by McGregor (1965)

Vasoconstriction was induced by mechanisms involving dii modes of calcium utilization viz: (i) Pharmaccnechanical pathway by low doses of the adrenergic neurotransm.itter, noradrenaline acting at - receptor; (ii) electromechanical pathway by 1.1 b potassium-and” (iip.) agents which facilitate Ca influx e.g.

A23187. !

The prostaglandins potentiated the vasoconstrictor effect

of NA. Potentiation factors calculated from different doses

of the prostaglandins showed the effects of the prostaglandins

to be dose - dependent and FGE^ to be significantly more potent

(P>0.005) than PGE,,a and PGI^* The prostaglandins failed to

potentiate high potassium - induced vasoconstriction. PChi^ also

failed to potentiate NA if the vasoconstrictor effects were

evoked in Ca~ - free Krebs solution; but the degree -of potentia

2+

tion increased with increase in the concentration of Ca 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 prejunctional since

cocaine, bretylium and reserpine pretreatment did not materially alter the effect of It was concluded that prostaglandins

potentiated HA vasoconstriction by facilitating Ca influx.

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The mechanism 'of this facilitation is discussed.

ITA vasoconstriction was competitively antagonised by adrenoceptor antagonists-phentolamine, tolazoline, yohimt• and phenoxybenzamine (in low concentrations). The blockade caused by these antagonists was reversed by PGE?. By comparing NA dose-ratios in the presence of antagonist with dose-ratios in

the nresence of antagonists plus different doses of PGB0, I

^

showed 1hat the degree of reversal was related to the dose of PGE. For example, the NA dose - ratio for yohimbine (1.28 x ICT^I)

o

was reduced from 26.6 + 0.9 to ^.7 + 0.1 when PGE^ (2.8 x 10 M)

was included in the perfusion fluid with the antagonist. The

reveio_< of antagonism was not due to a change in the binding

characteristics of the aj- adrenoceptor since pA^ values for the

antagonist were not significantly different (P^.0.05) when PGS was

included with the antagonists. Evidence is presented which suggests

that reversal of antagonism involved utilization of internally

bound calcium since reversal of antagonism occured even after 2+

the omission of Ca 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 the nans- if reversal was simply a reflection of the enhgresponsiveness of the vascular

muscle to NA.

iii -

In contrast to the "competitive” - adrenoceptor antagonists, did not reverse the block of ITA vasoconstriction

caused by phenoxybenzanine (high doses); verapamil, cinnarizine or prazosin. All these agents caused blockade of NA that was not competitive in'nature. Since noneof the competitive