Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice

In the current experiments, we determined the response of plasma renin concentration (PRC) to acute intraperitoneal administration of furosemide (40 mg/kg), hydralazine (2 mg/kg), isoproterenol (10 mg/kg), candesartan (50 [micro]g), or quinaprilate (50 [micro]g) in conscious wild-type (WT) and cyclooxygenase (COX)-2-/- mice on three different genetic backgrounds (mixed, C57BL/6, 129J). PRC was measured in plasma obtained by tail vein puncture. Basal PRC was significantly lower in COX-2-/- than WT mice independent of genetic background (51, 10, and 17% of WT in mixed, 129J, and C57BL/6). All five acute interventions caused significant increases of PRC in both COX-2+/+ and -/- mice, but the response was consistently less in COX-2-deficient mice (e.g., [DELTA]PRC in ng ANG I * [ml.sup.-1] * [h.sup.-1] caused by furosemide, isoproterenol, hydralazine, quinaprilate, or candesartan 4,699 [+ or -] 544, 3,534 [+ or -] 957, 2,522 [+ or -] 369, 9,453 [+ or -] 1,705, 66,455 [+ or -] 21,938 in 129J WT, and 201 [+ or -] 78, 869 [+ or -] 275, 140 [+ or -] 71, 902 [+ or -] 304, 2,660 [+ or -] 954 in 129J COX-2-/-). A low-NaCl diet and enalapril for 1 wk caused a 14-fold elevation of PRC in COX-2-/- mice and was associated with a greatly increased PRC response to acute furosemide ([DELTA]PRC 201 [+ or -] 78 before and 15,984 [+ or -] 2,397 after low Na/enalapril). As measured by radiotelemetry, blood pressure and heart rate responses to furosemide, hydralazine, isoproterenol, candesartan, or quinaprilate were not different between COX-2 genotypes. In conclusion, chronic absence of COX-2 reduces renin expression, release, and PRC and is associated with a reduced ability to alter PRC during acute stimulation regardless of the nature of the stimulus. COX-2 activity does not appear to be a mandatory and specific requirement for furosemide-stimulated renin secretion. furosemide; hydralazine; isoproterenol; quinaprilate; candesartan; genetic background; cyclooxygenase-2