Renal impairment in deoxycorticosterone acetate‐salt hypertensive rats

Summary: This study has compared renal function in deoxycorticosterone (DOCA)‐salt hypertensive Wistar rats (uninephrectomy followed by administration of DOCA 25 mg subcutaneously every fourth day and 1% NaCl in the drinking water) with various control rats using the isolated perfused kidney preparation. The systolic blood pressure of DOCA‐salt hypertensive rats was 180 ± 10 mmHg (uninephrectomy controls: 136 ± 9 mmHg) while normalization of calcium intake (DOCA‐Ca rats, 1% CaCl 2 in water) attenuated this increase (systolic blood pressure, 146 ± 5 mmHg). Renal mass corrected for body weight increased by 25% after uninephrectomy, 55% in uninephrectomized rats given NaCl, 152% in DOCA‐salt rats and 147% in DOCA‐Ca rats. At a renal perfusion pressure of 135 mmHg, isolated perfused kidneys from DOCA‐salt rats showed decreases of 48% in glomerular filtration rate and 69% in sodium excretion with an increase of 44% in renal vascular resistance compared with uninephrectomized rats. There were no significant differences in renal function between DOCA‐salt and DOCA‐Ca rats. Histological assessment of renal pathology showed proximal tubular hypertrophy and hyperplasia, marked focal distal tubular atrophy, interstitial fibrosis and glomerular hypercellularity in DOCA rats compared with UNX rats. Lesions were less obvious in UNX‐salt or DOCA‐Ca rats. The lack of direct correlation between alterations in function and pathology may be explained by the compensatory effect of remaining healthy or hypertrophied nephrons. Thus, the DOCA‐salt model of hypertension in rats is associated with marked structural kidney damage and severely decreased kidney function. Marked attenuation of systemic hypertension by normalizing calcium intake in DOCA‐salt rats did not prevent impairment of kidney function.