Enhanced sympathetic neurotransduction in the superior mesenteric artery in a rat model of heart failure: role of noradrenaline and ATP

Author(s)

Blanco-Rivero, Javier ^{[1, 2, 3, 4]} ; Couto, Gisele K. ^[4] ; Paula, Suliana M. ^[4] ; Fontes, Milene T. ^[4] ; Rossoni, V, Luciana

Affiliation

^[1] Univ Autonoma Madrid, Sch Med, Dept Physiol, Madrid - Spain

^[2] Ctr Biomed Res Network Cardiovasc Dis CiberCV, Madrid - Spain

^[3] Res Inst Univ Hosp Paz IdiPaz, Madrid - Spain

^[4] V, Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 320, n. 2, p. H563-H574, FEB 2021.
• Web of Science Citations: 0

Abstract

Heart failure (HF) is associated with neurohumoral activation, which in turn leads to an increased peripheral resistance. In mesenteric vasculature, perivascular innervation plays relevant role maintaining vascular tonus and resistance. Therefore, we aimed to determine the possible alterations in superior mesenteric artery (SMA) perivascular innervation function in HF rats. HF was induced by coronary artery occlusion in male Wistar rats, and sham-operated (SO) rats were used as controls. After 12 wk, a greater vasoconstrictor response to electrical field stimulation (EFS) was observed in endothelium-intact and endothelium-denuded SMA of HF rats. Alpha-adrenoceptor antagonist phentolamine diminished this response in a higher magnitude in HF than in SO animals. However, the noradrenaline (NA) reuptake inhibitor desipramine increased EFS-induced vasoconstriction more in segments from HF rats. Besides, EFS-induced NA release was greater in HF animals, due to a higher tyrosine hydroxylase expression and activity. P2 purinoceptor antagonist suramin reduced EFS-induced vasoconstriction only in segments from SO rats, and adenosine 5'-triphosphate (ATP) release was lower in HF than in SO. Moreover, nitric oxide (NO) synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) enhanced EFS-induced vasoconstriction in a similar extent in both groups. HF was not associated with changes in EFS-induced NO release or the vasodilator response to NO donor sodium nitroprusside. In conclusion, HF postmyocardial infarction enhanced noradrenergic function and diminished purinergic cotransmission in SMA and did not change nitrergic innervation. The net effect was an increased sympathetic participation on the EFS-induced vasoconstriction that could help to understand the neurotransduction involved on the control of vascular tonus in HF. NEW \& NOTEWORTHY This study reinforces the pivotal role of noradrenergic innervation in the regulation of mesenteric vascular tone in a rat model of heart failure. Moreover, our results highlight the counteracting role of ATP and NA reuptake, and help to understand the signaling pathways involved on the control of vascular tonus and resistance in heart failure postmyocardial infarction. (AU)

• FAPESP's process: 10/50048-1 - Cellular and functional bases of exercise in cardiovascular diseases
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/20303-0 - Evaluation of the influence of perivascular adipose tissue (PVAT) on vascular reactivity of the aorta of infarcted rats submitted to aerobic and resistance training
• Grantee: Milene Tavares Fontes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/22335-7 - Study of perivascular innervation in arteries from post-myocardial infarction rats: effect of physical training
• Grantee: Luciana Venturini Rossoni
• Support Opportunities: Research Grants - Visiting Researcher Grant - International