Effect of cyclo-oxygenase blockade on the renal actions of vasopressin and SK&F 105494 in the rhesus monkey.
1. Vasopressin administration to pentobarbitone-anaesthetized, hydrated female rhesus monkeys resulted in dose-dependent increases in urine osmolality and decreases in urine flow. Treatment with indomethacin at a dose (5 mg kg-1, i.v.) that reduced urinary prostaglandin E2 (PGE2) excretion by at least 70% did not alter these responses. 2. The vasopressin antagonist, SK&F 105494 (Pas1,6D-Tyr(Et)2Val4Arg7D-Arg8desGly9 arginine vasopressin; 10 micrograms kg-1), caused significant rightward shifts (P less than 0.05) of both the vasopressin-urine osmolality and the vasopressin-urine flow dose-response curves. Treatment with indomethacin did not alter these responses. 3. SK&F 105494 alone or after indomethacin treatment had minimal effects on urine osmolality and urine flow. 4. The data indicate that indomethacin does not alter the antidiuretic activity of vasopressin in the rhesus monkey and that SK&F 105494 is a potent antagonist of exogenous vasopressin with minimal agonist activity.
Brooks
D P
DP
SmithKline Beecham Pharmaceuticals, Department of Pharmacology, King of Prussia, PA 19406-0939.
Caldwell
N C
NC
Koster
P F
PF
Albrightson-Winslow
C R
CR
Kinter
L B
LB
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008253:Macaca mulatta; D009994:Osmolar Concentration; D014667:Vasopressins / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; C055736:SK&F 105494; D014667:Vasopressins; D001127:Arginine Vasopressin; D015232:Dinoprostone; D007213:Indomethacin