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Volume 2, Number 4, December 2001
Renin-angiotensin blockade improves renal cGMP production via non-AT2-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat
Nina Uhlenius, Olli Vuolteenaho, Ilkka Tikkanen Background:
To investigate the changes in the angiotensin II (Ang II) receptors and nitric oxide (NO)-cGMP pathway in the rat kidney after nitric oxide synthase (NOS) blockade.
Methods:
Captopril, an angiotensin-converting
enzyme (ACE) inhibitor, 20 mg/100 ml; and/or L-158,809 (an Ang II AT1-receptor
antagonist, 5 mg/100 ml) and L-NAME (NOS inhibitor, 50 mg/100 ml) were administered
orally for 12 weeks. Blood pressure (BP), urinary albumin, urinary cGMP excretion,
plasma ANP, and plasma renin activity were measured. In vitro autoradiography was
used to locate the Ang II receptors in the kidney.
Results:
Captopril and L-158,809 treatments
normalised BP and prevented the appearance of albuminuria in rats receiving L-NAME.
Urinary cGMP excretion was significantly increased in L-158,809-treated rats
compared with the non-treated group, suggesting that the dysfunctional NO
system may be activated by the treatment. AT1-receptor
binding in the kidney was inhibited to about 40% of the control value after administration
of L-158,809. The AT2-receptor binding
was inhibited to less than 15% of the control value. NOS inhibition had no effect
on receptor binding.
Conclusion:
Blockade of NOS causes hypertension
and renal damage. Treatment with an ACE inhibitor and/or Ang II receptor antagonist
prevented these changes equally effectively. The stimulatory effect of AT1-receptor
antagonism on cGMP production was not mediated by AT2-receptor-dependent
mechanisms, since renal AT2-receptor
binding density was suppressed following treatment with L-158,809. AT1-receptor
blockade per se favours activation of humoral pathways that stimulate cGMP
production potentially contributing to renal and vascular protection in hypertension
and chronic renal disease. JRAAS 2001;2:233-239. View full PDF article (open in new window)
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