Diverging vasorelaxing effects of C-type natriuretic peptide in renal resistance arteries and aortas of GC-A-deficient mice.

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Steinmetz M, Potthast R, Sabrane K, Kuhn M

Diverging vasorelaxing effects of C-type natriuretic peptide in renal resistance arteries and aortas of GC-A-deficient mice.

Regul Pept. 2004 Jun 15;119(1-2):31-7.

PubMed ID

15093694 [ View in PubMed

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Abstract

This study aimed to characterize the vasorelaxing effects of ANP, BNP and CNP in isolated renal resistance arteries (RRA) from wild-type mice and mice with either systemic (GC-A -/-) or smooth muscle-restricted deletion of GC-A (SMC GC-A KO). In RRA from wild-type (GC-A +/+) mice natriuretic peptides (NP) induced concentration-dependent vasorelaxations with the rank order of potency ANP>BNP>CNP. In RAA obtained from mice with systemic or smooth muscle-restricted deletion of GC-A, the effects of ANP and BNP were abolished. In contrast, CNP induced concentration-dependent vasorelaxations of GC-A -/- and SMC GC-A KO RRA. However, the efficacy of CNP for vasorelaxation was markedly diminished compared with wild-type RRA. Such changes in CNP responsiveness did not affect large arteries as the aorta and they were not due to vascular changes secondary to chronic arterial hypertension in GC-A -/- mice. Unaltered vasorelaxing effects of acetylcholine and sodium nitroprusside demonstrated unaltered function of downstream targets regulated by cGMP in vascular smooth muscle. An increased expression of the clearance receptor (NPR-C) or diminished expression of GC-B were not found to account for the differences in CNP responsiveness. In conclusion, observations in isolated aortic rings do not necessarily allow conclusions concerning the physiology of natriuretic peptides in the smaller resistance size arteries. Changes at the GC-B receptor level are likely to explain the diminished responsiveness of GC-A-deficient RRA to CNP.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Nitroprusside	Atrial natriuretic peptide receptor 1	Protein	Humans	Yes	Agonist	Details