(Hypertension. 2000;35:43.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Aging and Chronic Hypertension Decrease Expression of Rat Aortic Soluble Guanylyl Cyclase
From the Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt/Main, Germany.
Abstract—We analyzed the
influence of aging and genetic hypertension on the function and
expression of soluble guanylyl cyclase (sGC) in the aortas of
prehypertensive and old spontaneously hypertensive rats (SHR) as well
as in age-matched normotensive Wistar-Kyoto rats (WKY). The expression
of heterodimeric sGC (
1 and ß1) was
assessed at the mRNA and protein level, and its function was assessed
by the relaxant responses of phenylephrine-contracted
endothelium-denuded aortic rings to the nitric oxide
(NO) donor sodium nitroprusside. The vasodilator potency of sodium
nitroprusside was significantly reduced (P<0.05) with
age (3- to 6-fold increase in the EC50 in old WKY and SHR
compared with their young counterparts) as well as with hypertension
(3-fold increase in old SHR compared with age-matched WKY), whereas the
vasodilator potency of sodium nitroprusside did not differ between
young SHR and WKY. A similar influence of aging and hypertension on
NO-stimulated GC activity was revealed at the GC expression level:
Whereas the ß1 protein content was similar in young rats
of both strains, old WKY exhibited 60% lower and old SHR exhibited
80% lower ß1 subunit protein compared with young rats
(P<0.05). Moreover, the abundance of 1
and ß1 mRNA (assessed by reverse
transcriptase—polymerase chain reaction) was similar in young rats but
was 2.5-fold (1) and 4.3-fold (ß1) lower
in old SHR compared with old WKY. In conclusion, our findings show that
both aging and hypertension decrease sGC expression and its
NO-dependent activation in aortic tissue. Downregulation of sGC may
therefore contribute to arterial dysfunction in senescence
and chronic hypertension.
Key Words: aging • hypertension, genetic • guanylyl cyclase • aorta • nitric oxide
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