HYDROCHLOROTHIAZIDE EXACERBATES NITRIC OXIDE-BLOCKADE NEPHROSCLEROSISWITH GLOMERULAR HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective To determine whether a diuretic can also reverse the clinica l, systemic, renal and glomerular haemodynamic and pathological change s caused by nephrosclerosis. Methods Three groups of 20-week-old spont aneously hypertensive rats (SHR) were investigated: control male SHR; a similar group, administered 50 mg/l N-G-nitro-L-arginine methyl este r (L-NAME) for 3 weeks; and SHR treated similarly with L-NAME but also with 80 mg/kg per day hydrochlorothiazide (HCTZ) by gavage for 3 week s. Results The mean arterial pressure, cardiac output, effective renal plasma flow and glomerular filtration rate decreased as urinary volum e increased in the SHR treated with HCTZ and L-NAME, A micropuncture s tudy demonstrated increased glomerular capillary pressure (P-G, 56 +/- 1 versus 68 +/- 3 mmHg) associated with increased efferent (2.1 +/- 0 .2 versus 2.9 +/- 0.3 u) but no change in afferent arteriolar resistan ces compared with the SHR group treated with L-NAME only, In addition, HCTZ administration increased the juxtamedullary glomerular injury sc ore (47 +/- 13 versus 114 +/- 29) associated with elevated urinary pro tein excretion (35 +/- 1 versus 53 +/- 13 mg/100 g body weight per 24 h) The afferent arteriolar injury score was not changed, The P-G eleva tion was related not only to severe glomerulosclerosis but also to inc reased fibronectin and alpha-smooth muscle actin deposition. Conclusio n HCTZ administration exacerbated the changes in renal and micropunctu re dynamics, proteinuria and histopathological nephrosclerosis produce d by L-NAME in SHR.