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.

• Authors: Y Ono, H Ono, E D Frohlich
• Journal: Journal of hypertension (J Hypertens) Vol. 14 Issue 7 Pg. 823-8 (Jul 1996) ISSN: 0263-6352 [Print] England
• PMID: 8818920 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Diuretics
• Sodium Chloride Symporter Inhibitors
• Hydrochlorothiazide
• Nitric Oxide Synthase
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Antihypertensive Agents (pharmacology, therapeutic use)
• Diuretics
• Hemodynamics (drug effects)
• Hydrochlorothiazide (pharmacology, therapeutic use)
• Hypertension (chemically induced, drug therapy)
• Kidney (drug effects, pathology)
• Male
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nephrosclerosis (chemically induced, drug therapy, pathology, physiopathology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Proteinuria (drug therapy)
• Rats
• Rats, Inbred SHR
• Renal Circulation (drug effects)
• Sodium Chloride Symporter Inhibitors (pharmacology, therapeutic use)
• Vascular Resistance (drug effects)