Angiotensin II enhances β-adrenergic receptor-mediated vasorelaxation in aortas from young but not old rats

Abstract

beta-Adrenergic receptor (beta-AR)-mediated (cAMP-dependent) vasorelaxation declines with advancing age. It has been shown that angiotensin II (ANG II), a potent vasoconstrictor, enhances cAMP-mediated vasorelaxation. Therefore, we questioned whether ANG II could reverse age-related, impaired beta-AR-mediated vasorelaxation and cAMP production. Pretreatment of aortic rings from 6-wk-old or 6-mo-old male Fischer 344 rats with ANG II significantly enhanced vasorelaxation induced by isoproterenol (Iso), a beta-AR agonist, and forskolin, a direct activator of adenylyl cyclase, but not dibutyryl-cAMP or isobutylmethylxanthine. The ANG II effect was blocked by losartan but not PD-123319 and was not observed in the aortas from 12- and 24-mo-old animals. Iso-stimulated cAMP production in the aorta was enhanced in the presence of ANG II in the 6-wk-old and 6-mo-old age groups only. Results suggest ANG II cannot reverse the age-related impairment in beta-AR-dependent vasorelaxation. We conclude aging may affect a factor common to both ANG II-receptors and beta-AR signaling pathways or aging may impair cross-talk between these two receptor pathways.

Angiotensin II, a unique vasoactive agent dissociates myosin light chain phosphorylation from contraction

“…Since the AT-receptors are well known to be rapidly down-regulated [ 1 , 20 ], cessation of [Ca 2+ ] i increase may be due to the down-regulation of AT-receptors. We also found that the angiotensin II-induced contraction was completely inhibited by the AT 1 receptor antagonists, 1 µ M losartan [ 7 ] or 10 nM KRH-594 [ 28 ], supporting the results by Schutzer et al [ 27 ] in rat aortic tissue and by Castoldi et al . [ 6 ] in cultured rat aortic smooth muscle cells.…”

Phospholipase C and Src Modulate Angiotensin II-Induced Cyclic AMP Production in Preglomerular Microvascular Smooth-Muscle Cells From Spontaneously Hypertensive Rats

“…Also, in aortic rings from Fischer 344 rats, Ang II significantly enhances vasorelaxation induced by isoproterenol and enhances isoproterenol-induced cAMP production. 28 In contrast, in other model systems, Ang II either inhibits cAMP production or has no effect on cAMP production. For example, in human fetal mesangial cells, Ang II attenuates isoproterenol-induced cAMP production.…”

Biochemical and Molecular Aspects of Vascular Adrenergic Regulation of Blood Pressure in the Elderly

“…Therefore, changes in physiology could be due to age-related changes in the processing and degradation of cAMP through phosphodiesterases. We have determined that there are no age-related changes in general phosphodiesterase inhibitor-mediated vasorelaxation using 3-isobutyl-1-methylxanthine (IBMX), a nonspecific phosphodiesterase subtype inhibitory agent [ 62 ]. However, others [ 63 ] found that using a low dose of IBMX caused impaired cAMP accumulation in blood vessel preparation from older rats.…”

“…In terms of vasorelaxation being affected was a study that found that angiotensin II can enhance cAMP-mediated vasorelaxation via angiotensin II-type 1-receptors (AT 1 ) [ 96 ]. We examined the interaction among aging, β -AR-mediated vasorelaxation, and angiotensin II [ 62 ]. Our results showed that this effect of angiotensin II on agonist-mediated vasorelaxation was limited to young (6-week-old) or adult (6-month-old) rats, was absent in aged (12- and 24-month-old) animals, and was mediated by angiotensin II-type 1 receptors.…”