Excitatory effects of the vasodilator hydralazine on acoustic startle in the rat.
Several drugs that functionally depress noradrenergic transmission depress acoustic startle amplitude (e.g., clonidine, phenoxybenzamine). Since these agents also depress blood pressure, the current study was designed to investigate the effects of hypotension per se (in the absence of decreased noradrenergic transmission) on the acoustic startle response. The vasodilator hydralazine was chosen because it produces marked hypotension in conscious rats, yet results in a compensatory increase in noradrenergic transmission (sympathetic rebound), rather than a decrease, as is seen with many other hypotensive agents. Hydralazine (0.3-20 mg/kg, IP) produced a marked and long-lasting increase in startle amplitude, compared to saline-treated controls. In a similar group of subjects, IP administration of 2.5 mg/kg hydralazine decreased mean arterial blood pressure by about 50% in conscious rats. Since, at the doses and treatment times employed in the present study, hydralazine decreases blood pressure but not startle amplitude, these data suggest that there is no relationship between changes in blood pressure and changes in startle amplitude across all drugs. Moreover, since hydralazine-induced hypotension results in an increase in noradrenergic transmission (sympathetic rebound), these data are consistent with the hypothesis that increases in central noradrenergic transmission increase acoustic startle amplitude. Lastly, since the most prominent direct action of hydralazine occurs in the periphery, hydralazine may alter startle through central actions that are triggered in the periphery.
D000161:Acoustic Stimulation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D006830:Hydralazine; D009638:Norepinephrine