CIRCADIAN-RHYTHMS IN RENAL-FUNCTION IN HYPERTENSIVE TGR(MREN-2)27 RATS AND THEIR NORMOTENSIVE CONTROLS

Patients with secondary hypertension frequently display abnormal circa dian blood pressure profiles, characterized by a failure to decrease b lood pressure at night. The transgenic TGR(mRen-2)27 rat strain, devel oping fulminant hypertension after the mouse salivary Ren-2 renin gene has been integrated into its genome, provides a fundamental model of genetic hypertension, Because of an inverse circadian blood pressure p rofile and an unchanged rhythmic pattern of heart rate compared with t he normotensive Sprague-Dawley (SPR) strain, it was proposed to serve as an animal model of genetic hypertension. It was the aim of the pres ent study to investigate the circadian rhythmicity in renal function o f the transgenic rat to determine whether hypertension and disturbed c ircadian blood pressure profile would affect kidney function. Urinary water, electrolyte, and protein excretion, as well as glomerular filtr ation rate and renal plasma flow, were determined in unrestrained free ly moving transgenic hypertensive (TGR) and SPR normotensive control r ats by collecting urine and arterial blood every 4 h. Significant and similar circadian rhythms were found in renal excretion and hemodynami cs in both normotensive and hypertensive strains. Peaks occurred in th e active dark period, whereas troughs were found in daytime for all pa rameters. However, it has to be pointed out that, although the circadi an profiles were not grossly perturbed in hypertensive animals, some s mall differences between SPR and TGR strains did exist in renal functi on. These discrepancies were precisely related to acrophase, showing a slight phase delay, and also to relative amplitude in TGR. This study demonstrates that the inverted circadian blood pressure profile affec ted only slightly the circadian rhythms in kidney function in TGR comp ared with SPR. These findings support the notion that time-dependent c hanges in systemic blood flow may be of greater importance for circadi an regulation of kidney function than systemic blood pressure.