Involvement of central α 1- and α 2-adrenoceptors on cardiovascular responses to moxonidine

Abstract

In the present study we compared the effects produced by moxonidine (α 2-adrenoceptor/imidazoline agonist) injected into the 4th cerebral ventricle and into the lateral cerebral ventricle on mean arterial pressure, heart rate and on renal, mesenteric and hindquarter vascular resistances, as well as the possible action of moxonidine on central α 1- or α 2-adrenoceptors to produce cardiovascular responses. Male Holtzman rats ( n = 7–8) anesthetized with urethane (0.5 g/kg, intravenously — i.v.) and α-chloralose (60 mg/kg, i.v.) were used. Moxonidine (5, 10 and 20 nmol) injected into the 4th ventricle reduced arterial pressure (− 19 ± 5, − 30 ± 7 and − 43 ± 8 mmHg vs. vehicle: 2 ± 4 mmHg), heart rate (− 10 ± 6, − 16 ± 7 and − 27 ± 9 beats per minute — bpm, vs. vehicle: 4 ± 5 bpm), and renal, mesenteric and hindquarter vascular resistances. Moxonidine (5, 10 and 20 nmol) into the lateral ventricle only reduced renal vascular resistance (− 77 ± 17%, − 85 ± 13%, − 89 ± 10% vs. vehicle: 3 ± 4%), without changes on arterial pressure, heart rate and mesenteric and hindquarter vascular resistances. Pre-treatment with the selective α 2-adrenoceptor antagonist yohimbine (80, 160 and 320 nmol) injected into the 4th ventricle attenuated the hypotension (− 32 ± 5, − 25 ± 4 and − 12 ± 6 mmHg), bradycardia (− 26 ± 11, − 23 ± 5 and − 11 ±6 bpm) and the reduction in renal, mesenteric and hindquarter vascular resistances produced by moxonidine (20 nmol) into the 4th ventricle. Pre-treatment with yohimbine (320 nmol) into the lateral ventricle did not change the renal vasodilation produced by moxonidine (20 nmol) into the lateral ventricle. The α 1-adrenoceptor antagonist prazosin (320 nmol) injected into the 4th ventricle did not affect the cardiovascular effects of moxonidine. However, prazosin (80, 160 and 320 nmol) into the lateral ventricle abolished the renal vasodilation (− 17 ± 4, − 6 ± 9 and 2 ± 11%) produced by moxonidine. The results indicate that the decrease in renal vascular resistance due to moxonidine action in the forebrain is mediated by α 1-adrenoceptors, while the cardiovascular effects produced by moxonidine acting in the brainstem depend at least partially on the activation of α 2-adrenoceptors.