Effects of systemic and renal intramedullary endothelin-1 receptor blockade on tissue NO and intrarenal hemodynamics in normotensive and hypertensive rats

0565782 - FGÚ 2023 RIV NL eng J - Journal Article
Badzyńska, B. - Vaněčková, Ivana - Sadowski, J. - Hojná, Silvie - Kompanowska - Jezierska, E.
Effects of systemic and renal intramedullary endothelin-1 receptor blockade on tissue NO and intrarenal hemodynamics in normotensive and hypertensive rats.
European Journal of Pharmacology. Roč. 910, 5 Nov (2021), č. článku 174445. ISSN 0014-2999. E-ISSN 1879-0712
Grant - others:AV ČR(CZ) PAN-17-13
Program: Bilaterální spolupráce
Institutional support: RVO:67985823
Keywords : blood pressure * endothelin receptors * endothelin-1 * hypertension * nitric oxide * renal blood flow
OECD category: Cardiac and Cardiovascular systems
Impact factor: 5.195, year: 2021
Method of publishing: Open access
https://doi.org/10.1016/j.ejphar.2021.174445

Endothelin 1 (ET-1) seems essential in salt-dependent hypertension, and activation of ETA receptors causes renal vasoconstriction. However, the response in the renal medulla and the role of tissue NO availability has never been adequately explored in vivo. We examined effects of ETA and ETB receptor blockade (atrasentan and BQ788) on blood pressure (MAP), medullary blood flow (MBF) and medullary tissue NO. Effects of systemic and intramedullary blocker application were compared in anesthetized normotensive ET-1-pretreated Sprague-Dawley rats (S-D), in salt-dependent hypertension (HS/UNX) and in spontaneously hypertensive rats (SHR). Total renal blood flow (RBF) was measured using a Transonic renal artery probe, MBF as laser-Doppler flux, and tissue NO signal using selective electrodes. In normotensive rats ET-1 significantly increased MAP, decreased RBF (−20%) and renal medullary NO. In HS/UNX rats atrasentan decreased MAP and increased medullary NO, earlier and more profoundly with intravenous infusion. In SHR atrasentan decreased MAP, more effectively with intravenous infusion, the increase in tissue NO (∼10%) was similar with both routes, however, only intramedullary atrasentan increased MBF. No consistent responses to BQ788 were seen. We confirmed dominant role of ETA receptors in regulation of blood pressure and renal hemodynamics in normotensive and hypertensive rats and provided novel evidence for the role of ETA in control of intrarenal NO bioavailability in salt-dependent and spontaneous hypertension. Under conditions of activation of the endothelin system ETB stimulation preserved medullary perfusion.
Permanent Link: https://hdl.handle.net/11104/0337272