GLOMERULAR DYNAMICS AND MORPHOLOGY OF AGED SPONTANEOUSLY HYPERTENSIVERATS - EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION

Relationships between glomerular dynamics and renal injury, micropunct ure 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 (q uinapril; 3 mg/kg/day; for 3 weeks) groups. Urinary protein excretion (UPE) and histologic arteriolar (AIS) and glomerular (GIS) injury scor es were determined. Mean arterial pressure (MAP) of untreated SHR was increased compared with WKY (200+/-6 vs 119+/-4 mm Hg; P<0.01), effect ive renal plasma flow (ERPF) was reduced (1.47+/-0.21 vs 3.06+/-0.26 m l/min/per g; P>0.01), and filtration fraction (FF) and total renal vas cular resistance (RVR) of SHR were increased (P<0.01). Single-nephon p lasma flow (SNPF) of untreated SHR was decreased (174+/-17 vs 80+/-9 m l/min; P<0.01), and single-nephron filtration fraction and afferent ar teriolar resistance (R(A)) were increased (19.4+/-1.8 vs 30.0+/-2.5% a nd 1.90+/-0.25 vs 9.05+/-1.35 U, respectively; both P<0.01). Despite r educed SNPF, glomerular capillary pressure (P-G) increased (49.7+/-0.7 vs 53.8+/-1.3 mm Hg; P<0.05), the result of efferent arteriolar const riction (1.15+/-0.18 vs 2.84+/-0.36 U; P<0.01). Untreated SHR had high er UPE (13.9+/-1.5 vs 42.8+/-3.2; mg/100 g per day; P<0.01) and GIS an d 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 P-G decreased (to 49.1+/-1.1 mm Hg; P<0.01); in associat ion with R(A) and R(E) (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 highe r than in WKY. These data demonstrate that SHR naturally develop glome rular hypertension and ischemia with arteriolar constriction and glome rular sclerosis, and that intrarenal hemodynamic, pathologic, and prot einuric changes begin to reverse after 3 weeks of treatment.