Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice.
نویسندگان
چکیده
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 microg), or quinaprilate (50 microg) 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., DeltaPRC in ng ANG I x ml(-1) x h(-1) caused by furosemide, isoproterenol, hydralazine, quinaprilate, or candesartan 4,699 +/- 544, 3,534 +/- 957, 2,522 +/- 369, 9,453 +/- 1,705, 66,455 +/- 21,938 in 129J WT, and 201 +/- 78, 869 +/- 275, 140 +/- 71, 902 +/- 304, 2,660 +/- 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 (DeltaPRC 201 +/- 78 before and 15,984 +/- 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.
منابع مشابه
CALL FOR PAPERS Connexins and the Kidney Increased expression of cyclooxygenase 2 contributes to aberrant renin production in connexin 40-deficient kidneys
Wagner C, de Wit C, Gerl M, Kurtz A, Höcherl K. Increased expression of cyclooxygenase 2 contributes to aberrant renin production in connexin 40-deficient kidneys. Am J Physiol Regul Integr Comp Physiol 293: R1781–R1786, 2007. First published September 12, 2007; doi:10.1152/ajpregu.00439.2007.—We previously found that deletion of connexin 40 (Cx40) causes a misdirection of reninexpressing cells...
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ورودعنوان ژورنال:
- American journal of physiology. Renal physiology
دوره 292 1 شماره
صفحات -
تاریخ انتشار 2007