Laboratory Investigation

Kidney International (1987) 31, 718–724; doi:10.1038/ki.1987.57

Glomerular hypertension and injury in desoxycorticosterone–salt rats on antihypertensive therapy

Lance D Dworkin1, Helen D Feiner1 and Joseph Randazzo1

1Departments of Medicine and Pathology, New York University Medical Center, New York, New York, USA

Correspondence: Dr Dworkin, Department of Medicine, New York University Medical Center, 550 First Avenue, New York, New York 10016.

Received 31 January 1986; Revised 14 May 1986.

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Abstract

Glomerular hypertension and injury persist in desoxycorticosterone–salt rats on antihypertensive therapy. Uninephrectomized male Munich–Wistar rats received either weekly subcutaneous injections of vehicle and water for drinking; injections of desoxycorticosterone (DOC) and 1% saline (SALT) for drinking; or DOC and SALT with hydrochlorthiazide, hydralazine, reserpine and KC1 added. All studies were performed six weeks after UNX. At that time, rats receiving DOC and SALT alone were hypertensive and had significantly more proteinuria and morphologic evidence of glomerular injury than rats given vehicle and tap water which were normotensive. Antihypertensive therapy normalized mean arterial pressure in DOC-SALT rats, but failed to prevent proteinuria, mesangial expansion or focal segmental glomerular lesions. Micropuncture studies revealed that glomerular capillary pressure was elevated in both untreated and treated DOC-SALT animals. We conclude that drugs which successfully reduce systemic blood pressure may fail to correct glomerular capillary hypertension in DOC-SALT rats. As persistence of intrarenal hypertension is associated with significant glomerular injury, normalization of glomerular capillary pressure rather than systemic arterial pressure is crucial to the prevention of glomerular injury in this model.

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