Vasopressin-evoked [Ca2+](i) responses in neonatal rat cardiomyocytes

The presence of arginine vasopressin (AVP) V-1 receptors on neonatal rat ca rdiomyocytes (NRCs) linked to processes capable of elevating intracellular free calcium ([Ca2+](i)) is now firmly established. This study examined the sources and signaling involved in [Ca2+], elevations evoked by AVP in NRCs . AVP promoted increases in both [Ca2+](i) and 1,4,5-inositoltrisphosphate (IP3) levels in NRCs. The degree of [Ca2+](i) elevation was less than that of angiotensin II, but greater than that of endothelin-l. Extracellular Mg2 + depletion led to diminution of the maximal [Ca2+](i) response, with a rig htward shift in the concentration-response curves to AVP. The phospholipase C inhibitors, D-609, NCDC, or U73122, and the IP3 receptor blocker, hepari n, abolished the [Ca2+](i) response to AVP. Neither cyclooxygenase inhibiti on with indomethacin nor PKC inhibition with staurosporine had any effect. Neither ryanodine nor caffeine, which deplete sarcoplasmic reticulum (SR) C a2+ stores, nor ruthenium red, which inhibits both SR and mitochondrial Ca2 + stores, affected [Ca2+], responses to AVP. The SR Ca2+ pump inhibitor, cy clopiazonic acid, abolished, and removal of extracellular Ca2+ attenuated, the response to AVP. These data indicate that activation of cardiac V-1 rec eptors by AVP results in mobilization of Ca2+ from a distinct, non-SR, nonm itochonclrial, intracellular Ca2+ pool that is Ca2+ pump replenished and IP 3 sensitive. This process occurs secondary to phospholipase C (PLC)-mediate d generation of IP3, requires the presence of Mg2+ and extracellular Ca2+, and occurs in a manner independent of PKC and cyclooxygenase activation. Su ch mechanisms of Ca2+ mobilization might indicate a distinct role for AVP i n cardiac physiology and disease.