Although gender and oestrogen treatment influence production of the vasorelaxant, NO, their influence on factors downstream in the NO signal-transduction pathway, specifically protein kinase G (PKG), remains unknown. We aimed to study the influence of sex hormones on PKG, along with the endothelial modulation of these effects, in rat thoracic aortic rings in two separate groups, control male and female rats and ovariectomized female rats after treatment with oestrogen or vehicle. Vessel preparations were preconstricted with phenylephrine (0.1 μM). Constrictions were greater in male than female aortas. This differential effect was attenuated by endothelium removal, addition of the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1μM) and the nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (l-NMMA, 100 μM), supporting the role of NO in maintenance of basal relaxation and vascular tone in females. We have examined the relative activity of the specific PKG subtypes 1α and 1β in vascular smooth muscle, based on relaxation of rat aortas by two cGMP analogues with different selectivity, β-phenyl-l-N2-ethano-8-bromo-cGMP (8-Br-PET-cGMP) and 8-(2-aminophenylthio)cGMP (8-APT-cGMP). 8-Br-PET-cGMP was more potent than 8-APT-cGMP in both sexes, suggesting that PKG 1α is the primary subtype involved in vasorelaxation. The gender differences in PKG activity were examined based on relaxation responses in male and female rat aortas. Both 8-Br-PET-cGMP and 8-APT-cGMP were more potent in aortas from male than female rats. In further studies on the endothelial modulation of relaxation with 8-APT-cGMP, the differential gender-vasorelaxation response was negated by endothelium removal and addition of the guanylate cyclase inhibitor ODQ (1 μM), but not by the NOS inhibitor l-NMMA (100 μM), suggesting that an endothelial-dependent factor other than NO may be responsible for the observed differential PKG-mediated vasorelaxation between the sexes. To further investigate oestrogen influence on PKG, treated female rats were studied. Contrary to our hypothesis, in the presence of 1 μM ODQ, there were no differences in either the phenylephrine constriction, or the relaxation with 8-APT-cGMP from either sham-operated, vehicle-treated or oestrogen-treated ovariectomized rats. In conclusion, female rat aortas have greater basal NO production compared with males. Relaxant responses to PKG activation are greater in aortas from male compared with female rats. These findings suggest hormonal regulation of PKG; however, oestrogen treatment of ovariectomized rats did not affect PKG activity, suggesting factors other than oestrogen may be responsible for the gender differences noted in this study.
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Research Article|
March 29 2001
Gender differences in protein kinase G-mediated vasorelaxation of rat aorta
Helena TEEDE;
Helena TEEDE
*Prince Henry's Institute of Medical Research, P.O. Box 5152, Clayton 3168, Australia
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Andrea VAN DER ZYPP;
†Department of Medical Laboratory Science, RMIT University, P.O. Box 2476V, Melbourne, Victoria 3001, Australia
Correspondence: Dr Andrea van der Zypp (e-mail [email protected]).
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Henryk MAJEWSKI
Henryk MAJEWSKI
†Department of Medical Laboratory Science, RMIT University, P.O. Box 2476V, Melbourne, Victoria 3001, Australia
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Publisher: Portland Press Ltd
Received:
June 21 2000
Revision Received:
October 25 2000
Accepted:
January 16 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2001
2001
Clin Sci (Lond) (2001) 100 (5): 473–479.
Article history
Received:
June 21 2000
Revision Received:
October 25 2000
Accepted:
January 16 2001
Citation
Helena TEEDE, Andrea VAN DER ZYPP, Henryk MAJEWSKI; Gender differences in protein kinase G-mediated vasorelaxation of rat aorta. Clin Sci (Lond) 1 May 2001; 100 (5): 473–479. doi: https://doi.org/10.1042/cs1000473
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