Sodium chloride-induced partial inhibition in vivo of alpha 2-adrenoceptor agonist function.
Recent research has demonstrated that sodium diminishes the affinity of alpha 2-adrenoceptors for agonists in vitro. Clonidine, a highly specific agonist for alpha 2-receptors, has a transient hypertensive effect when administered parenterally. We studied in conscious anephric Wistar rats the effect of equimolar saline or mannitol solutions on the hypertensive response to clonidine administered subcutaneously in doses of 10, 100 and 1000 micrograms/kg body weight. Prior saline infusion reduced the hypertensive response to the two higher doses of clonidine by 65 and 70%, and displaced the slope of the dose-response curve downwards, but mannitol had no such effect. Pre-treatment with the alpha 2-antagonist yohimbine abolished the differences in clonidine-induced pressor response between saline-treated, mannitol-treated and control rats. On the contrary, after pre-treatment with the alpha 1-antagonist prazosin, the pressor action of clonidine was significantly reduced in the saline-infused rats compared to the other two groups. Thus the saline-induced blunting of the pressor response elicited by clonidine could be negated by prior alpha 2- but not alpha 1-blockade, indicating that sodium interfered with the stimulation of post-synaptic vascular alpha 2-adrenoceptors. These findings indicate that loading with sodium chloride attenuates the alpha 2-adrenoceptor function in vivo. Based on this, we suggest that the mechanism by which sodium excess causes a rise in blood pressure involves modification of the alpha 2-adrenoceptors.
Kohlmann
O
O
Gavras
I
I
Biollaz
J
J
Biollaz
B
B
Gavras
H
H
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009392:Nephrectomy; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012965:Sodium Chloride / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D008353:Mannitol; D012965:Sodium Chloride; D003000:Clonidine; D011224:Prazosin