Ca++ influx is essential for the hypotensive response to arginine vasopressin-induced neuron activation of the area postrema in the rat.
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.
Yang
Shu-Ju
SJ
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan 106, ROC.
Hwang
Ji-Chuu
JC
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
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