Effects of pinacidil on the sympatho‐adrenal system in dogs

Abstract

The aim of the present work was to study the antihypertensive effect of pinacidil, a potassium channel opener, in sinoaortic denervated (SAD) conscious dogs and to investigate whether the involvement of the sympathetic nervous system induced by this vasodilator compound is only of baroceptor reflex origin. Pinacidil (0.1, 0.2, 0.4 mg kg−1 i.v.) induced a dose‐dependent decrease in blood pressure in normal as well as in SAD dogs. In contrast, the induced‐tachycardia observed in normal dogs was not found in SAD animals. Since pinacidil induced an increase in plasma catecholamines, free fatty acids, glucose, plasma renin activity and aldosterone in SAD dogs, it is suggested that this sympathetic activation is independent of the baroreceptor reflex pathways. The sympathetic activation is mainly of peripheral origin, since pinacidil (0.7 mg kg−1 i.v.) induced an increase in adrenaline release from the adrenal gland after section of the great splanchnic nerve in anaesthetized dogs. This increase is probably due to an effect that does not involve K+ channel opening. However, this effect of pinacidil was not observed during splanchnic nerve stimulation (in this case, the involvement of K+ channel opening is suggested).

Renal morphological changes after sinoaortic denervation in dogs.

“…This result is in agreement with several previous data showing that this enhancement in plasma catecholamine level is strongly correlated with a decrease in leukocyte, cardiac, or renal £-adrenergic receptor number. 41 " 43 Moreover, we observed a decrease in plasma renin activity and a transient rise in urinary kallikrein activity, which were already reported in this model. 41 It can be suggested that these changes could be linked to the sympathetic hyperactivity and subsequent decrease in ^-adrenergic receptors.…”

“…During this second period of hypertension, urinary kallikrein activity 7 and renal /J-adrenergic receptor number 43 appeared to be reduced. This change in urinary kallikrein activity is in agreement with most of the data previously reported during hypertensive states in either humans 46 or experimental models.…”

“…Renal morphology was studied 1 (SAD 1, n=6) and 18 (SAD 18, n=5) months after sinoaortic denervation. Controls were by guest on May 11, 2018 http://hyper.ahajournals.org/ Downloaded from submitted to sham operation, and renal morphology was studied 1 (sham 1, n=4) and 18 (sham 18, n=4) months later. As previously reported by Damase-Michel et al, 11 sinoaortic denervation needed two successive surgical procedures.…”

“…Renal morphology was studied 1 (SAD 1, n=6) and 18 (SAD 18, n=5) months after sinoaortic denervation. Controls were by guest on May 11, 2018 http://hyper.ahajournals.org/ Downloaded from …”

Effects of cicletanine on vasoactive systems in conscious sinoaortic‐denervated dogs

“…Briefly, carotid and aortic nerves were cut under chloralose anaesthesia (80 mgkg iv) during two successive procedures, one at time 0 and the second one seven weeks later. This model of chronic hypertension in dogs, already allowed us to study mechanisms of actions of several antihypertensive drugs (Damase-Michel et al, 1987, 1989a, 1989b. The effectiveness of baroreceptor denervation was checked by the fajlure of noradrenaline (0.5, I , 2 p g k g iv) and phenylephrine (0.1, 1 and 10 p g k g iv) to induce bradycardia and nitroglycerin (1, 3, 10 and 30 p g k g iv) to induce tachycardia just after SAD and verified before any experiment in SAD animals.…”