Aging attenuates the vasodilator response to relaxin

Abstract

Relaxin, an insulin-like growth factor peptide, increases endothelium-dependent vasodilation and vascular compliance and decreases myogenic reactivity. These vascular effects significantly contribute to the physiological circulatory adaptations in pregnancy, particularly in the mesentery and kidney. Aging predisposes to vascular maladaptation and gestational hypertensive disease. We hypothesized that mild aging reduces the vascular responses to relaxin. In 20 young (10-12 wk) and 20 middle-aged (40-46 wk) female Wistar Hannover rats, vascular responses to chronic exposure of relaxin vs. placebo (5 days) were quantified in isolated mesenteric arteries and kidney. Vascular responses were evaluated using pressure-perfusion myograph, wire myograph, and an isolated perfused rat kidney model. Rxfp1 (relaxin family peptide) gene expression was determined by quantitative polymerase chain reaction. In young rats, relaxin stimulated nitric oxide (NO)-dependent flow-mediated vasodilation (2.67-fold, from 48 ± 9 to 18 ± 4 μl/min), reduced myogenic reactivity (from -1 ± 2 to 7 ± 3 μm/10 mmHg), and decreased mesenteric sensitivity to (28%, from 1.39 ± 0.08 to 1.78 ± 0.10 μM) but did not change compliance and renal perfusion flow (RPFF). In aged rats, relaxin did not affect any of the analyzed mesenteric or renal parameters. In aged compared with young placebo-treated rats, all mesenteric characteristics were comparable, while RPFF was lower (17%, from 6.9 ± 0.2 to 5.7 ± 0.1 ml·min⁻¹·100 g⁻¹) even though NO availability was comparable. Rxfp1 expression was not different among young and aged rats. Our findings suggest that moderate aging involves normal endothelial function but blunts the physiological endothelium-dependent and -independent vasodilator response to relaxin.

Relaxin induces rapid, transient vasodilation in the microcirculation of hamster skeletal muscle

“…Previous reports have indicated that relaxin simulates NOmediated responses in multiple vascular and non-vascular tissues , Novak et al 2002, Failli et al 2005, McGuane et al 2011, van Drongelen 2011. Our data show that TA and Branch arterioles dilate to the same extent relaxin, once the maximum size of the vessels is taken into account; however, MI arterioles do not respond directly to relaxin.…”

Effects of Relaxin on Arterial Dilation, Remodeling, and Mechanical Properties

“…In association with renal vasodilation, myogenic constriction of small renal arteries isolated from the relaxin-treated rats was inhibited, thus mimicking the inhibited myogenic constriction observed in small renal arteries from midterm pregnant rats [17,18]. When relaxin was administered to rats, flow-mediated vasodilation of isolated mesenteric arterioles was increased, analogous to midterm pregnancy [19,20]. However, this effect of relaxin was not observed in aged rats [20].…”

“…When relaxin was administered to rats, flow-mediated vasodilation of isolated mesenteric arterioles was increased, analogous to midterm pregnancy [19,20]. However, this effect of relaxin was not observed in aged rats [20]. Analogous to both midterm and late pregnancy [21][22][23], the renal vasoconstrictor response to an acute intravenous infusion of angiotensin II was attenuated in nonpregnant rats that were chronically administered relaxin [14].…”

Function and regulation of large conductance Ca2+-activated K+ channel in vascular smooth muscle cells

“…Vasorelaxation was attenuated with the advance of age [153]. Correspondingly, activity of BK Ca channels in VSMCs significantly decreased during aging [154,155].…”