Attenuation of noradrenergic neurotransmission by the thromboxane synthetase inhibitor, UK 38,485.

The purpose of this study was to determine the effects of chronic administration of the thromboxane synthetase inhibitor, UK 38,485, on noradrenergic neurotransmission. Male Sprague Dawley rats (n = 14) were treated once daily with either UK 38,485 (100 mg/kg; n = 7) or the vehicle of UK 38,485 (olive oil; n = 7) by gavage. The dose of UK 38,485 chosen was sufficient to inhibit ex vivo platelet TXB2 production by greater than 90% for 24 hours. One week into the treatment animals were prepared for in situ perfusion of their mesenteric vascular beds. Vasoconstrictor responses to both exogenous norepinephrine and periarterial nerve stimulation were determined both before and during an infusion of angiotensin II (9 ng/min) into the superior mesenteric artery. UK 38,485 significantly (P less than 0.02) attenuated the vascular response to periarterial nerve stimulation without altering the vascular response to either norepinephrine or angiotensin II. UK 38,485 did not influence the baseline perfusion pressure, the mean arterial blood pressure or the potentiation of neurotransmission by angiotensin II. These data indicate that in the in situ rat mesentery UK 38,485 attenuates the release of neurotransmitter from sympathetic nerve terminals.