Hydrochlorothiazide exacerbates nitric oxide-blockade nephrosclerosis with glomerular hypertension in spontaneously hypertensive rats.

Abstract:

OBJECTIVE:To determine whether a diuretic can also reverse the clinical, systemic, renal and glomerular haemodynamic and pathological changes caused by nephrosclerosis. METHODS:Three groups of 20-week-old spontaneously hypertensive rats (SHR) were investigated: control male SHR; a similar group, administered 50 mg/l NG-nitro-L-arginine methyl ester (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 weeks. RESULTS:The mean arterial pressure, cardiac output, effective renal plasma flow and glomerular filtration rate decreased as urinary volume increased in the SHR treated with HCTZ and L-NAME. A micropuncture study demonstrated increased glomerular capillary pressure (PG, 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 resistances compared with the SHR group treated with L-NAME only. In addition, HCTZ administration increased the juxtamedullary glomerular injury score (47 +/- 13 versus 114 +/- 29) associated with elevated urinary protein excretion (35 +/- 1 versus 53 +/- 13 mg/100 g body weight per 24 h) The afferent arteriolar injury score was not changed. The PG elevation was related not only to severe glomerulosclerosis but also to increased fibronectin and alpha-smooth muscle actin deposition. CONCLUSION:HCTZ administration exacerbated the changes in renal and micropuncture dynamics, proteinuria and histopathological nephrosclerosis produced by L-NAME in SHR.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Ono Y,Ono H,Frohlich ED

doi

10.1097/00004872-199607000-00004

subject

Has Abstract

pub_date

1996-07-01 00:00:00

pages

823-8

issue

7

eissn

0263-6352

issn

1473-5598

journal_volume

14

pub_type

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