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


CONCLUSIONS
HCTZ administration exacerbated the changes in renal and micropuncture dynamics, proteinuria and histopathological nephrosclerosis produced by L-NAME in SHR.
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Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121, USA.
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Frohlich
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D004232:Diuretics; D006439:Hemodynamics / Q000187:drug effects; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009400:Nephrosclerosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D014655:Vascular Resistance / Q000187:drug effects*
D000959:Antihypertensive Agents; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester