Hypotensive effect of clonidine during sodium depletion in the rat.
Clonidine was nonhypotensive in conscious unrestrained rats maintained on a normal sodium intake. In contradistinction, clonidine caused a dose-related hypotension in conscious unrestrained rats subjected to sodium depletion via furosemide. The plasma renin activity of normal and sodium-depleted rats was reduced after the administration of clonidine (100 mug/kg, iv) by 22.8% and 34.4%, respectively. Intravenous infusion of an angiotensin II antagonist, 1-Sar-8-Ala-angiotensin II, caused a significant reduction of arterial blood pressure in sodium-depleted rats but not in normal rats. Similarly, bilateral nephrectomy reduced arterial blood pressure and completely abolished the hypotensive effect of clonidine in sodium-depleted rats. Subcutaneous administration of chlorisondamine caused a significantly greater reduction of arterial blood pressure in sodium-depleted rats than it did in normal rats. Treatment of normal and sodium-depleted rats with 6-hydroxydopamine reduced the arterial blood pressure of both groups to approximately 85 mm Hg and completely abolished the hypotensive effect of clonidine in the sodium-depleted rats. The data presented in this paper are consistent with the conclusion that clonidine acts at some site in the sympathetic nervous system of sodium-depleted rats to inhibit renal nerve activity with a resultant suppression of renin secretion and a reduction of the angiotensin II-maintained arterial blood pressure. A similar sequence of events occurring in normal rats would not result in hypotension because their arterial blood pressure is not maintained by angiotensin II.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005665:Furosemide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced; D007010:Hyponatremia / Q000139:chemically induced*; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D009392:Nephrectomy; D051381:Rats; D012083:Renin / Q000494:pharmacology; D012504:Saralasin / Q000494:pharmacology
D006892:Hydroxydopamines; D005665:Furosemide; D012083:Renin; D012504:Saralasin; D003000:Clonidine