Calcium ATPase pump activity contributes more to cGMP- Than to cAMP- induced relaxations in rat aortic rings

Previous studies have demonstrated that cyclic nucleotides (cAMP and cGMP) stimulate the reuptake of calcium (Ca) into the sarcoplasmic reticulum (SR) via activation of the CaATPase pump. Calcium reuptake into the SR via CaATPase is thought to be the mechanism by which cAMP and cGMP induce relaxation. However, to our knowledge, the contribution of CaATPase pump activity in the relaxation responses to cAMP and cGMP has never been directly assessed. Hence, we tested the hypothesis that inhibition of CaATPase pump would prevent relaxation induced by cAMP and cGMP. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital and aortic rings were harvested for measurement of isometric force. Vessels were contracted with an EC₅₀ dose of phenylephrine and relaxed with cGMP or cAMP (10^-8 to 3×10^-5M) in the presence or absence of 10^-5M cyclopiazonic acid (CPA), an inhibitor of CaATPase. Our data indicate that cAMP in the presence of CPA resulted in 90% relaxation, whereas, cGMP resulted in 55% relaxation. From these data we can conclude: 1) cAMP and cGMP can induce relaxation by mechanisms other than activation of CaATPase activity and 2) CaATPase pump activity accounts for a greater proportion of relaxation induced by cGMP (45%) than cAMP (10%).