Involvement of central alpha1- and alpha2-adrenoceptors on cardiovascular responses to moxonidine.
In the present study we compared the effects produced by moxonidine (alpha2-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 alpha1- or alpha2-adrenoceptors to produce cardiovascular responses. Male Holtzman rats (n=7-8) anesthetized with urethane (0.5 g/kg, intravenously-i.v.) and alpha-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 alpha2-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 alpha1-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 alpha1-adrenoceptors, while the cardiovascular effects produced by moxonidine acting in the brainstem depend at least partially on the activation of alpha2-adrenoceptors.
Moreira
Thiago S
TS
Department of Physiology, Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Botucatu, 862, 04023-060, São Paulo, SP, Brazil. tsmoreira@fcr.epm.br
Takakura
Ana C
AC
Menani
José V
JV
Colombari
Eduardo
E
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C043482:moxonidine; D011224:Prazosin