Late gestational changes in sympathomimetic sensitivity in primagravid rabbit ligaments

The adrenoceptor profile of blood vessels supplying the medial collateral ligament (MCL) of virgin and primagravid (day 29 of pregnancy) rabbit knees was examined. Topical bolus administration of the α1-adrenoceptor agonists methoxamine and phenylephrine, and the α2-adrenoceptor agonist clonidine, to exposed knee joints resulted in a dose-dependent vasoconstriction of ligamentous vessels. The rank order of potency for the α-agonists was found to be phenylephrine > methoxamine > clonidine. Dobutamine, which acts on β1-adrenoceptors, and ritodrine, which is a β2-agonist, imparted a mild vasodilatatory effect on MCL blood vessels with the efficacy of ritodrine being greater than that of dobutamine. In primagravid rabbits, the constrictor effects of methoxamine and phenylephrine were significantly attenuated compared with virgin control animals (P < 0.0001), whereas clonidine-mediated vasoconstriction was unaltered in the gravid animal (P = 0.3957). With respect to β-adrenoceptor activity, the dilatational effect of dobutamine was the same as in controls (P = 0.5294), while ritodrine vasoactivity was completely abolished in primagravid knees (P < 0.005). These findings suggest that the adrenergic control of rabbit MCL blood flow is predominantly mediated by postjunctional α1and β2-adrenoceptors. Pregnancy leads to either downregulation and (or) desensitisation of α1and β2-adrenoceptors in the ligament which could disrupt normal joint homeostasis.