The adrenal medulla, not CB1 receptors, mediates the inhibitory effect of acute transverse aortic constriction on the neurogenic vasopressor response.

Abstract

Abstract Aims This study was performed to examine whether acute pressure overload induced by transverse aortic constriction (TAC) inhibits the neurogenic vasopressor response and, if so, to check the role of cannabinoid CB 1 receptors and/or other mechanisms. Main methods TAC or a sham operation was performed in pithed and vagotomised rats; sham-operated rats were infused with vasopressin to ensure a basal systolic blood pressure (SBP) comparable to that of TAC animals. SBP was increased by 40 mm Hg by electrical stimulation of the preganglionic sympathetic nerve fibres or phenylephrine injection. At the end of the experiments, the atria and aorta were isolated. Key findings TAC reduced the electrically (but not the chemically) induced pressor response by 80%; sham operation plus vasopressin had no effect. While the cannabinoid receptor agonist CP55940 and antagonists of CB 1 receptors (AM251), α 2 -adrenoceptors (rauwolscine) and K ATP channels (glibenclamide) did not modify the inhibitory effect of TAC, adrenal medulla removal did prevent this effect. The contractile effects of noradrenaline and isoprenaline were reduced (isolated left atria), whereas their chronotropic effects (right atria) were not affected by TAC, which also spared the vasoconstrictor responses to phenylephrine (isolated aorta). Significance Acute pressure overload induced by TAC reduces the neurogenic vasopressor response via an unknown presynaptic mechanism, an increase in heart rate induced by catecholamines released from the adrenal medulla and a decrease in the catecholamine-induced heart contractility. A better understanding of the negative consequences induced by the acute pressure overload may help in the design of future heart failure therapies.