title: Ca++ influx is essential for the hypotensive response to arginine vasopressin-induced neuron activation of the area postrema in the rat.
abstract: 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 x 10(-5) IU) microinjected into the AP 0.2 mm rostral to the CS of the midline was abolished by V(1A) 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 V(1A) 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.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan 106, ROC.
authors.forename: Shu-Ju
authors.initials: SJ
authors.lastname: Yang
authors.forename: Ji-Chuu
authors.initials: JC
authors.lastname: Hwang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D031608:Area Postrema / Q000166:cytology*; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008845:Microinjections / Q000379:methods; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002121:Calcium Channel Blockers; D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D001127:Arginine Vasopressin; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D002118:Calcium