Evidence that some imidazoline derivatives inhibit peripherally the vasopressor sympathetic outflow in pithed rats.
Imidazoline derivatives (e.g. clonidine and moxonidine) and alpha(2)-adrenoceptor agonists (e.g. B-HT 933) have been shown to inhibit sympathetically-induced [(3)H]noradrenaline release in several isolated blood vessels. The present study has compared the potential capability of agonists at imidazoline I(1/2) receptors and/or alpha(1/2)-adrenoceptors to inhibit the sympathetically-induced vasopressor responses in pithed rats. For this purpose, male Wistar rats were pithed and prepared for measurement of diastolic blood pressure and heart rate. Then, the vasopressor responses induced by either selective electrical stimulation (2 ms, 60 V; 0.03, 0.1, 0.3, 1 and 3 Hz) of the vascular sympathetic outflow (T(7)-T(9)) or i.v. bolus injections of exogenous noradrenaline (0.03, 0.1, 0.3, 1 and 3 microg/kg) were determined before and during i.v. continuous infusions of the agonists B-HT 933 (alpha(2)), clonidine (alpha(2), I(1)), moxonidine (alpha(2), I(1)), cirazoline (alpha(1), I(2)), agmatine (putative endogenous ligand of imidazoline receptors) and methoxamine (alpha(1)), or equivalent volumes of physiological saline. Electrical sympathetic stimulation elicited frequency-dependent vasopressor responses which were significantly inhibited during the continuous infusions of B-HT 933, clonidine, moxonidine, cirazoline and agmatine, but not of physiological saline. Interestingly, the vasopressor responses to exogenous noradrenaline, which remained unaffected during the infusions of physiological saline, B-HT 933, moxonidine, cirazoline and agmatine, were significantly blocked during the infusions of clonidine or methoxamine. These results suggest that B-HT 933, moxonidine, cirazoline and agmatine induced a prejunctional inhibition of the vasopressor sympathetic outflow in pithed rats, whilst clonidine inhibited the vasopressor sympathetic outflow by both prejunctional and postjunctional mechanisms.
Monroy-Ordoñez
E B
EB
Departamento de Farmacobiología, Cinvestav-Coapa, Czda. Tenorios 235, Col. Granjas-Coapa, 14330 México DF, Mexico.
Villalón
C M
CM
Cobos-Puc
L E
LE
Márquez-Conde
J A
JA
Sánchez-López
A
A
Centurión
D
D
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000376:Agmatine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001808:Blood Vessels / Q000294:innervation*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D054755:Imidazoline Receptors / Q000819:agonists; D048288:Imidazolines / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008729:Methoxamine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D001381:Azepines; D007093:Imidazoles; D054755:Imidazoline Receptors; D048288:Imidazolines; D000376:Agmatine; C043482:moxonidine; C015603:azepexole; D008729:Methoxamine; D003000:Clonidine; C014282:cirazoline