Acute hemodynamic responses to intravenous and intra-arterial guanethidine

Abstract

Intravenous administration of guanethidine to dogs causes an abrupt fall in systemic arterial pressure which is followed by a sustained increase. These studies were made to determine the nature of this biphasic response. Observations were made on dogs before and at frequent intervals after guanethidine was given. A fall in arterial pressure, an increase in cardiac output, and a decrease in peripheral resistance were observed within 10 sec; these changes lasted 40–50 sec. After the depressor phase, blood pressure and stroke volume increased while resistance returned to control levels. These acute changes subsided within 10–15 min. Ganglionic blockade augmented the pressor response and adrenergic blockade reduced it. Intra-arterial injection of guanethidine into perfused denervated forelegs caused brief vasodilatation followed by vasoconstriction. This response was qualitatively different from that seen with intra-arterial injection of norepinephrine. The results support indirectly the hypothesis that the systemic pressor response is caused by circulating catecholamines. The results demonstrate also that the drug has a local vasodilator action on the blood vessels of the foreleg.

Vasodilator Action of Guanethidine

“…A reflex increase in cardiac output would result from Circulation Rtsearch, Volume XI, November 196S vasodilatation. In these and in other experiments, 4 however, guanethidine had a direct vasodilator action on denervated forelegs; further, it increased cardiac output after ganglion-blocking drugs. 4 It appears that interference with sympathetic transmission is not the only mechanism which could explain these effects.…”

“…In these experiments, treatment with reserpine prevented the increases in cardiac output and heart rate. Hence, the cardiac-stimulating effects, which were observed during the depressor as well as the pressor phase in untreated animals, 4 appear to be caused by a local release of cate- …”

“…The vasodilator effect of intravenous guanethidine was transient in untreated animals, 4 and became sustained when the pressor response was prevented by depletion of norepinephrine. Systemic arterial pressure remained significantly lower than the control levels after the initial depressor phase when 4 mg./ Kg.…”

Adrenergic Neuron Blocking Drugs

“…Guanethidine (ABBOUD et al, 1961(ABBOUD et al, , 1962MCCUBBIN et al, 1961;POLLARD and BECK, 1971) and bretylium (BLAIR et al, 1960;GREEN, 1962) have a direct vasodilator action on blood vessels which can be observed in man and animals when their indirect sympathomimetic action has waned or when reserpine has been used to deplete endogenous stores of norepinephrine. ABBOUD et al (1961) studied the hemodynamic effects of intravenous guanethidine in dogs pretreated with reserpine.…”

“…ABBOUD et al (1961) studied the hemodynamic effects of intravenous guanethidine in dogs pretreated with reserpine. They also studied the action of intra-arterial guanethidine in the perfused foreleg of dogs.…”