Nephrotoxic serum nephritis with hypertension: amelioration by antihypertensive therapy.
We have examined the effects of antihypertensive therapy on glomerular dynamics and on the clinical and morphologic features of a model of nephrotoxic serum nephritis (NSN) in which hypertension occurs. NSN was induced in uninephrectomized male Sprague Dawley rats, which drank 0.9% sodium chloride ad libitum. One-half were assigned randomly to a treated group whose blood pressure was normalized on a regimen of reserpine, hydralazine, and hydrochlorothiazide. Hypertension continued throughout the 6 weeks of study in untreated rats (blood pressure 148 +/- 5 vs. 103 +/- 3 mm Hg in treated rats, P less than 0.01). Urinary protein excretion was greater (437 +/- 110 vs. 254 +/- 81 mg/24 hr, P less than 0.005), and serum albumin lower (1.6 +/- 0.4 vs. 2.9 +/- 0.3 g/dl, P less than 0.01) in hypertensive animals. Diffuse glomerular endo- and extracapillary proliferation and arteriolar medial hypertrophy were observed frequently in nephritic rats with untreated hypertension. By contrast, structural abnormalities were limited primarily to focal segmental proliferation involving fewer than one-third of glomeruli in the absence of vascular changes in treated normotensive rats. Micropuncture studies performed 8 to 16 days after induction of nephritis showed a reduction in glomerular capillary pressure (46 +/- 1 vs. 55 +/- 1 mm Hg, P less than 0.001), glomerular plasma flow rate (115 +/- 20 vs. 160 +/- 20 nl/min, P less than 0.01), and single nephron filtration rate (42 +/- 4 vs. 56 +/- 5 nl/min, P less than 0.001) with antihypertensive treatment, suggesting that a hemodynamic mechanism may have been responsible for enhanced glomerular injury in the hypertensive nephritic animals.
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004044:Dietary Proteins / Q000008:administration & dosage; D005919:Glomerular Filtration Rate; D006830:Hydralazine / Q000627:therapeutic use; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006977:Hypertension, Renal / Q000178:diet therapy / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000098:blood supply; D008297:Male; D009393:Nephritis / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D012110:Reserpine / Q000627:therapeutic use
D000959:Antihypertensive Agents; D004044:Dietary Proteins; D006852:Hydrochlorothiazide; D006830:Hydralazine; D012110:Reserpine