Effects of guanethidine on the blood pressure response to splanchnic nerve stimulation in the rat: role of the adrenal medulla

Abstract

1. Splanchnic nerve stimulation provokes a larger increase in blood pressure in intact rats than in rats previously demedullated by means of expression of the adrenals in situ and adrenalectomy followed by adrenocortical grafting. 2. Rats pretreated with guanethidine showed an attenuated albeit prolonged hypertensive response to splanchnic stimulation. Similar effects were exerted by guanethidine in rats demedullated by expression. In rats demedullated by grafting, smaller doses of guanethidine induced a more substantial depression of the blood pressure response without increasing its duration. 3. It is concluded that inhibition of the peripheral sympathetic endings induced by guanethidine was partially compensated by the enhancement of the cardiovascular effects of the mediators released by the adrenal medulla and that demedullation by expression did not completely eliminate chromaffin tissue.The role of the adrenal medulla in the pressor response to splanchnic nerve stimulation and in the changes induced by different drugs on this response have previously been studied by comparing splanchnic nerve stimulation before and after acute ablation or vascular exclusion of the suprarenal glands (Nickerson & Goodman, 1947;De Vleeschhouwer, 1935). Thus it has been observed that acute adrenalectomy abolishes the pressor response to splanchnic stimulation which is still present in cats after administration of guanethidine; hence it has been concluded that the arterial hypertension, evoked by splanchnic stimulation in cats treated with guanethidine, is due to the release of mediators from the adrenal medulla (Abercrombie & Davies, 1963). A reliable quantitative evaluation of the adrenomedullary contribution to the pressor effects of splanchnic stimulation cannot, however, be made by this experimental procedure. In fact, acute adrenalectomy involves a variable and often severe degree of surgical trauma which may in itself affect the cardiovascular reactivity non-specifically. Moreover, numerous early side effects of guanethidine (Maxwell, Plummer, Schneider, Povalski & Daniel, 1960) may obscure its principal pharmacological action, consisting of the inactivation of the sympathetic nerve terminals, which is still present some hours after the administration of the drug (Chang, Costa & Brodie, 1965). In the present work, therefore, the effects of guanethidine pretreatment on the pressor response to splanchnic stimulation were compared in intact and chronically adrenal demedullated rats. The results obtained in rats which had undergone adrenal demedulla-

Blood Pressure Responses to Adrenal Field Stimulation as a Measure of Adrenal Catecholamine Release

“…The present experiments have shown that the initial vasoconstrictor response does not quantitatively influence the second component caused by the release of medullary amines. This represents a definite improvement over direct splanchnic nerve stimulation which, in the rat, has been shown to cause wide-spread neurogenic vasoconstriction (Carpi & Cartoni, 1968). Indeed, guanethidine reduced the response to splanchnic nerve stimulation indicating that the neurogenic vasoconstrictor component was so extensive as to preclude any precise quantitation of the catecholamines released from the adrenal medulla.…”

“…However, splanchnic nerve stimulation also evokes a neuronally mediated vasoconstrictor response in the splanchnic vascular bed which forms a considerable component of the blood pressure response in the rat. In adrenalectomized rats with grafts of adreno-cortical tissue (Carpi & Cartoni, 1968) the blood pressure responses to low frequency splanchnic nerve stimulation remained unaltered, while at higher frequencies, they were still 60 to 65% of that obtained in the intact control rats. In the present work the blood pressure response to direct electrical stimulation of the whole adrenal gland of pithed rats was analyzed for its usefulness as an indicator of adrenomedullary hormone release without interference by vasoconstrictor neurones.…”

“…These two effects would account for the biphasic blood pressure response. An initial vasoconstrictor component to splanchnic nerve stimulation has been reported in various species (De Vleeschhouwer, 1935;Nickerson & Goodman, 1947;Abercrombie & Davies, 1963), including the rat (Carpi & Cartoni, 1968). These responses would be expected to be fast in onset and short in duration, compared with a response resulting from medullary catecholamine release.…”

“…The initial component of the blood pressure response to adrenal field stimulation was shown to be neurogenic vasoconstriction (Carpi & Cartoni, 1968). Indeed, guanethidine reduced the response to splanchnic nerve stimulation indicating that the neurogenic vasoconstrictor component was so extensive as to preclude any precise quantitation of the catecholamines released from the adrenal medulla.…”