Impairment of the autoregulation of renal hemodynamics and of the pressure-natriuresis relationship precedes the development of hypertension in Cyp1a1-Ren-2 transgenic rats

Objective The present study was performed to characterize the autoregulatory efficiency of renal blood flow and glomerular filtration rate and the pressure-natriuresis relationship in transgenic rats with inducible angiotensin II (ANG II)-dependent hypertension (Cyp1a1-Ren-2 rats). Methods The renin gene was induced in Cyp1a1-Ren-2 rats through dietary administration of the natural xenobiotic indole-3-carbinol (13C, 0.3%) for 12 and 24 h, respectively. Noninduced rats served as controls. Anesthetized rats were prepared for renal function studies and an aortic clamp was placed above the junction of the left renal artery to regulate the level of renal arterial pressure. Plasma renin activity, ANG II and aldosterone levels were measured at the end of the experiment by radioimmunoassay. Results Administration of 13C resulted in progressive increases in plasma renin activity and plasma and kidney ANG II levels; however, it did not significantly alter aldosterone levels as compared with those in noninduced rats. 13C induction for 12h did not cause significant changes in blood pressure as compared with those in noninduced rats. 13C induction for 24 h elicited a significant rise in blood pressure. Twelve-hour 13C induction caused an impairment of the autoregulatory efficiency of renal blood flow and glomerular filtration rate and of the pressure-natriuresis relationship as compared with that in noninduced rats. In addition, 24 h 13C induction of the renin gene resulted in a marked reduction in renal blood flow and glomerular filtration rate and a further impairment of the pressure-natriuresis mechanism as compared with that in noninduced rats. Conclusion Our findings indicate that an impairment of the pressure-natriuresis mechanism precedes the development of ANG II-dependent hypertension in Cyp1a1-Ren-2 transgenic rats. J Hypertens 27:575-586 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.