Circadian rhythms in renal function in hypertensive TGR(mRen-2)27 rats and their normotensive controls

Patients with secondary hypertension frequently display abnormal circadian blood pressure profiles, characterized by a failure to decrease blood pressure at night. The transgenic TGR(mRen-2)27 rat strain, developing 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 profile and an unchanged rhythmic pattern of heart rate compared with the normotensive Sprague-Dawley (SPR) strain, it was proposed to serve as an animal model of genetic hypertension. It was the aim of the present study to investigate the circadian rhythmicity in renal function of the transgenic rat to determine whether hypertension and disturbed circadian blood pressure profile would affect kidney function. Urinary water, electrolyte, and protein excretion, as well as glomerular filtration rate and renal plasma flow, were determined in unrestrained freely moving transgenic hypertensive (TGR) and SPR normotensive control rats by collecting urine and arterial blood every 4 h. Significant and similar circadian rhythms were found in renal excretion and hemodynamics in both normotensive and hypertensive strains. Peaks occurred in the active dark period, whereas troughs were found in daytime for all parameters. However, it has to be pointed out that, although the circadian profiles were not grossly perturbed in hypertensive animals, some small differences between SPR and TGR strains did exist in renal function. 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 affected only slightly the circadian rhythms in kidney function in TGR compared with SPR. These findings support the notion that time-dependent changes in systemic blood flow may be of greater importance for circadian regulation of kidney function than systemic blood pressure.