In-vitro contraction of the equine aortic valve.

The equine aortic valve is subject to non-inflammatory degenerative changes, associated with aortic valvular regurgitation (AR). This disease shares pathological and epidemiological features with AR in humans, and may serve as a useful model to study in-vitro functional responses associated with aging and disease. The study aim was to determine the contractile properties of the normal equine aortic valve. The contractile responses of equine aortic valves to angiotensin II, the thromboxane-mimetic U44069, endothelin-1, 5-hydroxytryptamine and the alpha-adrenoceptor agonists medetomidine, norepinephrine and phenylephrine were studied in vitro in organ baths. Selective antagonists were used to confirm the receptors involved. The order of potency of the agents causing contraction of equine aortic valve segments was angiotensin II > endothelin-1 > U44069 > medetomidine norepinephrine phenylephrine. 5-Hydroxytryptamine did not cause contraction of the equine aortic valve. The contractile response to angiotensin II was abolished by the AT1 receptor antagonist Sar1-Ile8-Angiotensin II, and that of U44069 by the thromboxane TXA2 receptor (TP) antagonist SQ29548. The contractile effects of endothelin-1 were blocked by the ET(A) receptor antagonist BQ123, but not by the ET(B) receptor antagonist BQ788. Yohimbine inhibited the contractile effects of phenylephrine, suggesting an alpha-2 adrenoceptor-mediated response. Equine aortic valves contract in response to a number of physiologically important endocrine, paracrine and neuronal mediators. Regulation of valvular tone could therefore be important in the normal functioning of the valve, and further understanding of these mechanisms may lead to insights into the pathophysiology of naturally occurring equine aortic insufficiency. In this respect, the horse should be considered as a model of the human condition.