Related Experiment Videos
Unilateral ureteral obstruction increases glomerular soluble guanylyl cyclase activity
K A McDowell1, R L Chevalier, B A Thornhill
1Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, USA.
Journal of the American Society of Nephrology : JASN
|November 1, 1995
Summary
Unilateral ureteral obstruction (UUO) in rats enhances glomerular cGMP accumulation due to reduced phosphodiesterase activity. Angiotensin II receptors modulate this response, suggesting a role for soluble guanylyl cyclase in counteracting UUO-induced vasoconstriction.
Area of Science:
- Nephrology
- Physiology
- Molecular Biology
Background:
- Unilateral ureteral obstruction (UUO) reduces renal blood flow (RBF) and glomerular filtration rate (GFR).
- Vasodilatory mechanisms, including nitric oxide synthase (NOS) activity, attempt to counterbalance vasoconstriction during UUO.
- The role of soluble guanylyl cyclase (sGC) stimulation in UUO-related renal changes requires further investigation.
Purpose of the Study:
- To investigate differences in sGC stimulation between glomeruli from obstructed and normal kidneys.
- To determine the impact of phosphodiesterase (PDE) activity on cGMP accumulation in UUO glomeruli.
- To explore the influence of angiotensin II receptors on the sGC pathway in UUO.
Main Methods:
- Isolation of glomeruli from Sprague-Dawley rats subjected to 24-hour UUO or sham operation.
- Measurement of intracellular and extracellular cyclic guanosine monophosphate (cGMP) using radioimmunoassay (RIA) after stimulation with sodium nitroprusside (SNP).
- Assessment of PDE activity and modulation by PDE inhibitors (isobutyl methylxanthine) and angiotensin II receptor blockers (losartan).
Main Results:
- UUO glomeruli exhibited significantly greater extracellular cGMP accumulation in response to SNP compared to sham glomeruli.
- Reduced PDE activity in UUO glomeruli contributed to enhanced cGMP accumulation.
- Angiotensin II receptor blockade with losartan attenuated the SNP-induced cGMP response in UUO glomeruli, indicating receptor modulation.
Conclusions:
- Decreased PDE activity in UUO glomeruli enhances the accumulation of extracellular cGMP following sGC stimulation.
- Angiotensin II receptors play a modulatory role in this response.
- sGC may be involved in counteracting angiotensin II-mediated vasoconstriction during UUO, preserving renal function.