Vasopressin-Evoked [Ca2+]i Responses in Neonatal Rat Cardiomyocytes

The presence of arginine vasopressin (AVP) V1 receptors on neonatal rat cardiomyocytes (NRCs) linked to processes capable of elevating intracellular free calcium ([Ca]i) is now firmly established. This study examined the sources and signaling involved in [Ca]i elevations evoked by AVP in NRCs. AVP promoted increases in both [Ca]i and 1,4,5-inositoltrisphosphate (IP3) levels in NRCs. The degree of [Ca]i elevation was less than that of angiotensin II, but greater than that of endothelin-1. Extracellular Mg depletion led to diminution of the maximal [Ca]i response, with a right-ward shift in the concentration-response curves to AVP. The phospholipase C inhibitors, D-609, NCDC, or U73122, and the IP3 receptor blocker, heparin, abolished the [Ca]i response to AVP. Neither cyclooxygenase inhibition with indomethacin nor PKC inhibition with staurosporine had any effect. Neither ryanodine nor caffeine, which deplete sarcoplasmic reticulum (SR) Ca stores, nor ruthenium red, which inhibits both SR and mitochondrial Ca stores, affected [Ca]i responses to AVP. The SR Ca pump inhibitor, cyclopiazonic acid, abolished, and removal of extracellular Ca attenuated, the response to AVP. These data indicate that activation of cardiac V1 receptors by AVP results in mobilization of Ca from a distinct, non-SR, nonmitochondrial, intracellular Ca pool that is Ca pump replenished and IP3 sensitive. This process occurs secondary to phospholipase C (PLC)-mediated generation of IP3, requires the presence of Mg and extracellular Ca, and occurs in a manner independent of PKC and cyclooxygenase activation. Such mechanisms of Ca mobilization might indicate a distinct role for AVP in cardiac physiology and disease.