Impaired effect of relaxin on vasoconstrictor reactivity in spontaneous hypertensive rats

Relaxin is thought to be involved in vasodilation to pregnancy by increasing endothelium-dependent vasodilation and compliance, and decreasing myogenic reactivity. Primary (essential) hypertension predisposes to circulatory maladaptation and subsequent gestational hypertensive disease. This study aimed to determine that vascular responses to chronic exposure to relaxin are impaired in young female rats with primary hypertension. In 10-12 weeks old Wistar-Hannover rats (WHR) and spontaneous hypertensive rats (SHR), we determined vascular responses in isolated kidney and mesenteric arteries after 5-days of chronic exposure to relaxin (4 μg/h) or placebo. SHR show decreased sensitivity to phenylephrine (by 67%, p<0.01) and renal perfusion flow (RPFF, by 19%, p<0.01), but no changes in flow-mediated vasodilation, myogenic reactivity or vascular compliance. In WHR, relaxin stimulated flow-mediated vasodilation (2.67 fold, from 48 ± 9 to 18 ± 4 μl/min, p = 0.001), inhibited myogenic reactivity (from -1 ± 2 to 7 ± 3 μm/10 mmHg, p = 0.01), and decreased sensitivity to phenylephrine (28%, from 1.39 ± 0.08 to 1.78 ± 0.10 μM, p<0.01), but left compliance and RPFF unchanged. NO-blockade by L-NAME diminished most relaxin-mediated responses. In SHR, the vasodilator effects of relaxin were blunted for myogenic reactivity and sensitivity to phenylephrine, with similar effects on flow-mediated vasodilation, compliance, RPFF and equal Rxfp1 (relaxin family peptide receptor) gene expression, as compared to WHR. Primary hypertension blunts both the relaxin-induced inhibition of myogenic reactivity and α-adrenergic vasoconstrictor response, independent from Rxfp1 gene expression, while the relaxin-dependent enhanced flow-mediated vasodilation remains intact. This implies selective resistance to relaxin in young subjects suffering from primary hypertension.