Differential effects of sulindac on renal hemodynamics and function in the rat.
Renal hemodynamics were studied using an electromagnetic perivascular flow sensor in anesthetized rats injected i.v. with vehicle, 5 or 10 mg/kg body weight (b.w.) sulindac. No hemodynamic changes occurred with vehicle (n = 6), but mean arterial pressure was significantly decreased (by 15 mmHg) with sulindac (n = 12). In the 5 mg/kg b.w. sulindac group (n = 7), renal blood flow progressively and significantly increased from 7.88 +/- 0.36 to 8.98 +/- 0.58 ml/min, except during concomitant intrarenal infusion of 3 mg/kg b.w. per h proadifen (n = 7). The pressure limits for efficient and no renal blood flow autoregulation remained unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/kg b.w. sulindac group (n = 5), renal blood flow did not change but autoregulatory pressure limits were lowered by 10 mmHg 2 h after treatment (P < 0.025). Also, Na+ retention was marked. Prostanoid excretion in urine was significantly reduced with either dose but basal plasma renin activity was not (about 8 ng/ml per h; n = 15). When plasma renin activity was enhanced after a reduction in renal perfusion pressure (n = 21), it was decreased from 11.5 +/- 1.2 to 7.4 +/- 0.2 ng/ml per h only by 10 mg/kg b.w. sulindac (P < 0.05; n = 6). In conclusion, differential effects of sulindac on renal hemodynamics, Na+ excretion and plasma renin activity were demonstrated. Renal hemodynamic changes could be related in part to the cytochrome P-450 arachidonic acid pathway.
Kramp
R A
RA
Service de Physiologie et Pharmacologie, Faculté de Médecine, Université de Mons-Hainaut, Mons, Belgium.
Caron
N
N
Genard
J
J
Lejeune
C
C
Gulbis
E
E
Herman
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D011188:Potassium / Q000097:blood / Q000652:urine; D011335:Proadifen / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood / Q000652:urine; D013467:Sulindac / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D014867:Water; D013467:Sulindac; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D012964:Sodium; D011335:Proadifen; D012083:Renin; D011188:Potassium