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 weeks) and 20 middle aged (40-46 weeks) female Wistar Hannover rats, vascular responses to chronic exposure of relaxin versus placebo (5 days) were quantified in isolated mesenteric arteries and kidney. Vascular responses were evaluated using pressure-perfusion myograph, wire myograph and isolated perfused rat kidney model (IPRK). Rxfp1 (relaxin family peptide) gene expression was determined by qPCR. 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), 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 to 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/100g) even though NO-availability was comparable. Rxfp1 expression was not different amongst 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.
- Wistar-Hannover rats
- mesenteric arteries
- Isolated Perfused Rat Kidney
- human recombinant relaxin
- Copyright © 2010, American Journal of Physiology - Heart and Circulatory Physiology