Characteristics of depression by clonidine of the pressor response to alpha 1-adrenoceptor agonists in pithed rats.
Effects of clonidine on the elevated arterial diastolic blood pressure induced by infusion of alpha 1-adrenoceptor agonists were studied in pithed rats. Intravenous injection of clonidine resulted in a dose-dependent pressor response at a resting state and a further increase in the moderately elevated diastolic blood pressure induced by infusion of lower doses of phenylephrine and methoxamine. However, clonidine produced a depressor response when diastolic blood pressure was elevated by around 100 mmHg during infusion of higher doses of alpha 1-adrenoceptor agonists. The depressor response to clonidine was dose-dependent at a dose range of 10 to 1000 micrograms/kg. On the other hand, clonidine failed to cause the depressor response while diastolic pressure was elevated by infusion of vasopressin by around 100 mmHg. NG-methyl-L-arginine, a nitric oxide synthase inhibitor, and propranolol, a beta-adrenoceptor antagonist, did not affect the depressor response to clonidine. After pretreatment with yohimbine, an alpha 2-adrenoceptor antagonist, the depressor response to clonidine was inhibited, but prazosin, an alpha 1-adrenoceptor antagonist, did not suppress the depressor response. These results demonstrate that clonidine specifically depresses the pressor response to alpha 1-adrenoceptor agonists in pithed rats via a mechanism which is not mediated by beta-adrenoceptors and independent of endothelium-dependent relaxing factor, and suggest that a yohimbine-sensitive mechanism may be related to the clonidine effect.
Nomura
S
S
Tsukuba Research Laboratories, Upjohn Pharmaceuticals Limited, Ibaraki, Japan.
Sunagane
N
N
Uruno
T
T
Kubota
K
K
D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D003655:Decerebrate State / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008729:Methoxamine / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D008729:Methoxamine; D003000:Clonidine