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Facilitation by the renin-angiotensin system of cyclosporine-evoked hypertension in rats: Role of arterial baroreflexes and vasoreactivity

Nasser, Suzanne A.; Sabra, Ramzi; Elmallah, Ahmed I.; Ei-Din, Mahmoud M. Mohy; Khedr, Mohamed M.; El-Mas, Mahmoud M.

Authors

Ramzi Sabra

Ahmed I. Elmallah

Mahmoud M. Mohy Ei-Din

Mohamed M. Khedr

Mahmoud M. El-Mas



Contributors

Abstract

Aims
Cyclosporine (CSA) elevates blood pressure (BP) and alters arterial baroreflex sensitivity (BRS) and vasoreactivity. In this study we determined whether the renin-angiotensin system (RAS) interplays with other vasopressor pathways in mediating the CSA actions.

Materials and methods
Whole animal and isolated vascular preparations were employed to determine the effects of pharmacologic interruption of angiotensin II (Ang II), endothelin (ET), or thromboxane (TXA2) signaling on the adverse cardiovascular effects of CSA.

Key findings
CSA (25 mg/kg/day i.p. for 7 days) caused significant increases in BP that were paralleled with (i) reduced BRS measured by phenylephrine (BRSPE) or sodium nitroprusside (BRSSNP), (ii) enhanced aortic contractile responses to Ang II and U-46619 (thromboxane analogue), and (iii) reduced aortic eNOS expression and acetylcholine, but not SNP, vasorelaxations. Except for the reduced BRSSNP, the CSA effects disappeared upon concurrent administration of losartan (angiotensin AT1 receptor antagonist), captopril (angiotensin converting enzyme inhibitor), or their combination. Moreover, CSA augmentation of Ang II contractions was abolished after cyclooxygenase inhibition (indomethacin) or endothelin ETA/ETB receptor blockade (atrasentan/BQ788). By contrast, the blockade of thromboxane receptors (terutroban) failed to alter the CSA-evoked facilitation of Ang II responsiveness.

Significance
The facilitation of baroreflex control and inhibition of vascular responsiveness to Ang II and thromboxane contribute to the BP lowering effect of RAS inhibitors in CSA-treated rats. Further, endothelin receptors and vasoconstrictor prostanoids contribute to the CSA-evoked exaggeration of Ang II vascular responsiveness and hypertension.

Citation

Nasser, S. A., Sabra, R., Elmallah, A. I., Ei-Din, M. M. M., Khedr, M. M., & El-Mas, M. M. (2016). Facilitation by the renin-angiotensin system of cyclosporine-evoked hypertension in rats: Role of arterial baroreflexes and vasoreactivity. Life Sciences, 163, 1-10. https://doi.org/10.1016/j.lfs.2016.08.024

Journal Article Type Article
Acceptance Date Aug 25, 2016
Online Publication Date Aug 26, 2016
Publication Date Oct 15, 2016
Deposit Date Mar 7, 2024
Journal LIFE SCIENCES
Print ISSN 0024-3205
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 163
Pages 1-10
DOI https://doi.org/10.1016/j.lfs.2016.08.024