Involvement of the renin-angiotensin system in captopril-induced sodium appetite in the rat.
The angiotensin converting enzyme inhibitor, captopril, given to rats in their drinking water (about 40 mg/day) for 6 days caused an increase in intake of hypertonic NaCl solution which began 1-2 days after the captopril was started and reached a plateau after 4-5 days. Twice-daily subcutaneous injections of captopril (15 mg per injection) elicited a sodium appetite similar in pattern to that seen with oral administration. The rats remained in sodium and fluid balance during oral captopril treatment and the haematocrit did not alter. Captopril infused directly into the ventricles (12 micrograms/h), or captopril reaching the brain from the periphery across a leaky blood-brain barrier, suppressed the sodium appetite which normally follows oral captopril. Continuous intravenous infusion of captopril at rates high enough to block angiotensin converting enzyme in the brain (25, 50 or 500 mg/day) did not cause sodium appetite. As soon as the rate was reduced to a low value (5 mg/day), NaCl intake increased. In conclusion, moderate levels of circulating captopril which do not cross the blood-brain barrier in sufficient amounts to block cerebral angiotensin converting enzyme, result in an increase in circulating angiotensin I which stimulates sodium appetite when it is converted to angiotension II in the brain.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects*; D006400:Hematocrit; D007263:Infusions, Parenteral; D007276:Injections, Intraventricular; D008297:Male; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*; D012964:Sodium / Q000652:urine; D012965:Sodium Chloride / Q000008:administration & dosage*; D013997:Time Factors; D014882:Water-Electrolyte Balance
D000806:Angiotensin-Converting Enzyme Inhibitors; D012462:Saline Solution, Hypertonic; D012965:Sodium Chloride; D011392:Proline; D002216:Captopril; D012964:Sodium