Hydralazine: Effect on the Outflow of Noradrenaline and Mechanical Responses Evoked by Sympathetic Nerve Stimulation of the Rat Tail Artery

Abstract

1 The effects of hydralazine on the vasoconstrictor responses to field stimulation of sympathetic nerves were studied in the isolated proximal segments of the rat tail artery. Vasoconstrictor responses to transmural stimulation were depressed by superfusion of hydralazine (0.3, 3 and 30pM) in a concentration-dependent manner. The inhibition appeared slowly and was not easily reversed by washing.2 Hydralazine (30 nm, 0.3 and 3 gM) reduced the stimulation-induced overflow of tritium from proximal and distal segments of the tail artery labelled with [3H]-noradrenaline in a concentrationdependent manner. This phenomenon appeared rapidly and was easily reversed by washing. 3 Theophylline (0.5 mM) did not affect the inhibitory effect of hydralazine on the stimulation-induced tritium efflux from the distal segment of the rat tail artery. 4 The present results indicate that hydralazine has, in addition to its action on vascular smooth muscle, a very marked effect on sympathetic nerve terminals. The mechanism of this presynaptic inhibition appears to be different from the postsynaptic effect, in view of the much shorter delay, the shape of the dose-effect curve, and the lack of interaction with theophylline.

Hydralazine Reduces the Quantal Size of Secretory Events by Displacement of Catecholamines From Adrenomedullary Chromaffin Secretory Vesicles

“…30 Conversely, Chevillard et al 31 report that HYD, in a range of concentrations that are similar to those used in the present study, reduces 3 [H]-noradrenaline output from sympathetic nerve terminals.…”

Hydrallazine: Mode of Action at the Neuroarterial Junction

“…The methods used for the study of the postand pre-junctional effects have been published by Worcel (1978) and Chevillard, Mathieu, Saiag & Worcel (1980) respectively. The noradrenaline concentration in arteries was measured as follows: after excision, the arterial segments were blotted lightly and weighed.…”

Increased plasma norepinephrine accompanies persistent tachycardia after hydralazine.

“…In conclusion, hydralazine appears to possess only weak tyramine-like properties. " 20 Chevillard et al 21 studied the effects of hydralazine on the release of 3 H-NE from the isolated rat tail artery during field stimulation. Concentrations hydralazine equivalent to those observed in plasma of hypertensive patients after intravenous 22 or oral 23 administration inhibited the overflow of tritium caused by electrical stimulation at 10 Hz.…”