Details

Autor(en) / Beteiligte

• Holtwick, Rita
• Gotthardt, Michael
• Skryabin, Boris
• Steinmetz, Martin
• Potthast, Regine
• Zetsche, Bernd
• Hammer, Robert E.
• Herz, Joachim
• Kuhn, Michaela

Titel

Smooth Muscle-Selective Deletion of Guanylyl Cyclase-A Prevents the Acute but not Chronic Effects of ANP on Blood Pressure

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2002-05, Vol.99 (10), p.7142-7147

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• Atrial natriuretic peptide (ANP) is an important regulator of arterial blood pressure. The mechanisms mediating its hypotensive effects are complex and involve the inhibition of the sympathetic and renin-angiotensin-aldosterone (RAA) systems, increased diuresis/natriuresis, vasodilation, and enhanced vascular permeability. In particular, the contribution of the direct vasodilating effect of ANP to the hypotensive actions remains controversial, because variable levels of the ANP receptor, guanylyl cyclase A (GC-A), are expressed in different vascular beds. The objective of our study was to determine whether a selective deletion of GC-A in vascular smooth muscle would affect the hypotensive actions of ANP. We first created a mutant allele of mouse GC-A by flanking a required exon with loxP sequences. Crossing floxed GC-A with SM22-Cre transgene mice expressing Cre recombinase in smooth muscle cells (SMC) resulted in mice in which vascular GC-A mRNA expression was reduced by ≈80%. Accordingly, the relaxing effects of ANP on isolated vessels from these mice were abolished; despite this fact, chronic arterial blood pressure of awake SMC GC-A KO mice was normal. Infusion of ANP caused immediate decreases in blood pressure in floxed GC-A but not in SMC GC-A knockout mice. Furthermore, acute vascular volume expansion, which causes release of cardiac ANP, did not affect resting blood pressure of floxed GC-A mice, but rapidly and significantly increased blood pressure of SMC GC-A knockout mice. We conclude that vascular GC-A is dispensable in the chronic and critical in the acute moderation of arterial blood pressure by ANP.