Renal vascular effects of antihypertensive therapy in uninephrectomized SHR.
Serial determinations of protein excretion rate and systolic blood pressure (SBP) were made in spontaneously hypertensive rats (SHR) uninephrectomized (UNX) at six weeks of age and given tap water (CON), or water with hydrochlorthiazide, hydralazine and reserpine (HHR), captopril (CAP) or enalapril (ENP). Compared to CON, significant hypertension was prevented, kidney weight was lower and there was less proteinuria in HHR, CAP and ENP rats followed for 30 weeks after UNX. Morphologic studies of these four groups revealed that antihypertensive therapy reduced the incidence of glomerular sclerosis in UNX SHR by 50%. Despite complete absence of systemic hypertension, there was striking medial thickening of lobular arteries and arterioles of rats given the angiotensin converting enzyme (ACE) inhibitor, captopril. These vascular abnormalities were present to a lesser degree in rats given ENP, but were entirely absent in untreated animals or in those ingesting the HHR combination. Micropuncture studies performed five weeks after UNX in four additional groups of CON, HHR, CAP and ENP rats revealed that glomerular capillary pressure was elevated in CON and reduced by all three drug regimens. These studies support the hypothesis that glomerular capillary hypertension and/or nephron hypertrophy predispose to glomerular injury in this model of hypertension and reduced renal mass. ACE inhibitors and HHR are equivalent in their ability to prevent glomerular hypertension and damage in these rats, but the former, and in particular captopril, produce abnormalities of cortical vessels via a mechanism not dependent on the presence of systemic hypertension.
Dworkin
L D
LD
Department of Medicine, New York University Medical Center, New York.
Grosser
M
M
Feiner
H D
HD
Ullian
M
M
Parker
M
M
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use; D004656:Enalapril / Q000627:therapeutic use; D006830:Hydralazine / Q000627:therapeutic use; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000235:genetics; D007668:Kidney / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000187:drug effects*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects; D012110:Reserpine / Q000627:therapeutic use
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D006830:Hydralazine; D004656:Enalapril; D012110:Reserpine; D002216:Captopril