We attempted to relate the signal pathway to the hypotension induced by arginine vasopressin (AVP) injection into the area postrema (AP) in urethane-anesthetized and ventilated rats with vagotomy. A femoral artery and vein were catheterized to measure the blood pressure (BP) and administer drugs, respectively. The rat was placed on a stereotaxic apparatus to expose the calamus sriptorius (CS) by craniostomy and maintained at normocapnia in hyperoxia. In protocol 1, hypotension evoked by AVP (3.0 × 10- 5 IU) microinjected into the AP 0.2 mm rostral to the CS of the midline was abolished by V1A antagonist, U73122 (phospholipase C blocker), and BAPTA-AM (Ca++ chelator), suggesting that an increasing intracellular Ca++ is essential for AVP-induced hypotension. In protocol 2, AVP-induced hypotension was abolished by EGTA (extracellular Ca++ chelator) and Ca++ blockers such as nifedipine, nimodipine (L-types), and omega-conotoxin MVIIC (P/Q-type), but not by omega-conotoxin GVIA (N-type). In protocol 3, AVP-induced hypotension was blocked by calphostin C (protein kinase C inhibitor) and mimicked by an increase in intracellular K+ ions that was reversed by EGTA. Vehicle injections produced no changes in BP. In protocol 4, glutamate-induced hypotension was reversed by BAPTA-AM but not by EGTA or V1A antagonist. Our data suggest that AVP-induced hypotension depends on Ca++ influx through a signal pathway from phospholipase C to protein kinase C which inactivates K+ channels that may depolarize AP neurons to activate L- and P/Q-type Ca++ channels. This may provide new insights into establishing a relationship between the signal pathway and physiological functions.
ASJC Scopus subject areas
- 神經科學 (全部)