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(Hypertension. 1995;25:207-213.)
© 1995 American Heart Association, Inc.
Articles |
Glomerular Dynamics and Morphology of Aged Spontaneously Hypertensive Rats
Effects of Angiotensin-Converting Enzyme Inhibition
From the Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, La.
Correspondence to Edward D. Frohlich, MD, Alton Ochsner Medical Foundation, 1516 Jefferson Hwy, New Orleans, LA 70121.
Abstract Relationships between glomerular dynamics and renal injury, micropuncture and histological studies were assessed in 73 week-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats divided into untreated and angiotension-converting enzyme inhibitor–treated (quinapril; 3 mg/kg/day; for 3 weeks) groups. Urinary protein excretion (UPE) and histologic arteriolar (AIS) and glomerular (GIS) injury scores were determined. Mean arterial pressure (MAP) of untreated SHR was increased compared with WKY (200±6 vs 119±4 mm Hg; P<0.01), effective renal plasma flow (ERPF) was reduced (1.47±0.21 vs 3.06±0.26 ml/min/per g; P>0.01), and filtration fraction (FF) and total renal vascular resistance (RVR) of SHR were increased (P<0.01). Single-nephron plasma flow (SNPF) of untreated SHR was decreased (174±17 vs 80±9 ml/min; P<0.01), and single-nephron filtration fraction and afferent arteriolar resistance (RA) were increased (19.4±1.8 vs 30.0±2.5% and 1.90±0.25 vs 9.05±1.35 U, respectively; both P<0.01). Despite reduced SNPF, glomerular capillary pressure (PG) increased (49.7±0.7 vs 53.8±1.3 mm Hg; P<0.05), the result of efferent arteriolar constriction (1.15±0.18 vs 2.84±0.36 U; P<0.01). Untreated SHR had higher UPE (13.9±1.5 vs 42.8±3.2; mg/100 g per day; P<0.01) and GIS and AIS scores than WKY (4.3±1.1 vs 64.3±8.4 and 16.6±3.1 vs 96.3±14.4; both P<0.01). Quinapril reduced SHR MAP (to 173±7 mm Hg), FF and RVR (all P<0.01) and increased ERPF (to 2.40±0.26 ml/min per g; P<0.05), and PG decreased (to 49.1±1.1 mm Hg; P<0.01); in association with RA and RE (to 5.18±0.8 U; P<0.01 and 1.74±0.31 U; P<0.05). Although quinapril reduced UPE (to 23.6±1.8 mg/100 g per day; P<0.01) with GIS and AIS (P<0.05) in SHR, these indices remained higher than in WKY. These data demonstrate that SHR naturally develop glomerular hypertension and ischemia with arteriolar constriction and glomerular sclerosis, and that intrarenal hemodynamic, pathologic, and proteinuric changes begin to reverse after 3 weeks of treatment.
Key Words: intrarenal hemodynamics • renal micropunctures • aging • rats, inbred SHR • rats, inbred WKY • nephrosclerosis • angiotensin-converting enzyme inhibitors • proteinuria • quinapril
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