Comparison of Cardiovascular Actions of Dihydralazine, Phentolamine, and Prazosin in Spontaneously Hypertensive Rats

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Intravenous administration of dihydralazine, phentolamine, or prazosin (0.3 mg/kg) produced similar decreases in blood pressure in pentobarbital-anesthetized spontaneously hypertensive rats (SHR), as well as in pithed SHR whose blood pressure had been raised by an i.v. infusion of cirazoline or by electrical spinal cord stimulation. However, only dihydralazine produced vasodilatation in pithed SHR with blood pressure unaltered or elevated by an i.v. infusion of vasopressin, and this effect was not modified by atropine, propranolol, or promethazine. In pithed SHR the pressor responses to norepinephrine or electrical stimulation of the spinal cord were less inhibited after phentolamine than after prazosin (0.3 mg/kg, i.v.). Furthermore, only phentolamine induced a significantly smaller blockade of responses to electrical spinal cord stimulation than to exogenous norepinephrine. The 5-hydroxytryptamine pressor responses were significantly reduced by both i.v. methysergide (5 μg/kg) and phentolamine (1.0 mg/kg), but were unchanged or slightly enhanced by prazosin (0.3 and 1.0 mg/kg). In pithed normotensive rats with a sustained sympathetic tachycardia produced by thoracic spinal cord stimulation, i.v. clonidine increased blood pressure and lowered heart rate. Intravenous phentolamine (1.0 mg/kg) competitively antagonized both effects of clonidine, whereas prazosin (1.0 and 5.0 mg/kg) or dihydralazine (1.0 mg/kg) affected only the clonidine pressor responses. These results indicate that in the rat prazosin inhibits vascular postsynaptic α-adrenoceptors and lacks the direct vascular smooth muscle relaxant activity possessed by dihydralazine. Prazosin differed from phentolamine in that it inhibited the pressor responses to endogenous and exogenous norepinephrine similarly and interfered neither with cardiac presynaptic α-adrenoceptors nor with vascular postsynaptic 5-hydroxytryptamine receptors.

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