Characterization of β-adrenoceptor-mediated relaxation signals in isolated pulmonary artery of Dahl salt-sensitive hypertensive and normotensive rats

Abstract

1 Relaxant responses to isoprenaline (ISO) were studied in the pulmonary arteries of normotensive and hypertensive Dahl salt-sensitive rats. Rats were fed either a high-salt (4.0%) or low-salt (0.14%) diet for 5 weeks. Animals fed a high-salt diet (167/123 ± 2/2 mmHg) had a significantly higher blood pressure compared to those fed a low-salt diet (127/87 ± 2/2 mmHg).

2 Isoprenaline-elicited relaxations were not significantly different in tissues from hypertensive compared to normotensive animals. Responses to ISO were significantly attenuated in denuded tissues and substantially more so in hypertensive compared to normotensive animals. While relaxant responses to ISO were resistant to inhibition by N^ω-nitro-l-arginine methyl ester, indomethacin, glibenclamide or a combination of barium chloride and ouabain, they were inhibited by Rp-cAMP, anandamide and acidic buffer. The inhibitory impact of anandamide and acidic buffer was significantly greater in tissues from hypertensive vs. normotensive rats.

3 The resting membrane potential (E_m) of smooth muscle cells was −67.0 ± 0.7 mV (n = 43 cells) and −66.6 ± 0.8 mV (n = 55 cells) in pulmonary arteries from hypertensive and normotensive rats, respectively. Isoprenaline produced hyperpolarization of E_m which was significant in the blood vessels of hypertensive (−71.6 ± 0.8 mV; n = 29 cells) but not normotensive (−68.1 ± 0.7 mV; n = 49 cells) rats.

4 The endothelium plays a critical role in β-adrenoceptor-mediated relaxation but nitric oxide is not the mediator for the response. It is possible that the greater hyperpolarization caused by ISO in blood vessels from hypertensive compared to normotensive rats is mediated by activation of TASK-1 channels.