HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 102/4/1402    most recent 00825.2006v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Henderson, K. K. Articles by Byron, K. L. Search for Related Content PubMed PubMed Citation Articles by Henderson, K. K. Articles by Byron, K. L.

Vasopressin-induced vasoconstriction: two concentration-dependent signaling pathways

Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Maywood, Illinois

Submitted 26 July 2006 ; accepted in final form 2 January 2007

Current scientific literature generally attributes the vasoconstrictor effects of [Arg⁸]vasopressin (AVP) to the activation of phospholipase C (PLC) and consequent release of Ca²⁺ from the sarcoplasmic reticulum. However, half-maximal activation of PLC requires nanomolar concentrations of AVP, whereas vasoconstriction occurs when circulating concentrations of AVP are orders of magnitude lower. Using cultured vascular smooth muscle cells, we previously identified a novel Ca²⁺ signaling pathway activated by 10–100 pM AVP. This pathway is distinguished from the PLC pathway by its dependence on protein kinase C (PKC) and L-type voltage-sensitive Ca²⁺ channels (VSCC). In the present study, we used isolated, pressurized rat mesenteric arteries to examine the contributions of these different Ca²⁺ signaling mechanisms to AVP-induced vasoconstriction. AVP (10^–14–10^–6 M) induced a concentration-dependent constriction of arteries that was reversible with a V_1a vasopressin receptor antagonist. Half-maximal vasoconstriction at 30 pM AVP was prevented by blockade of VSCC with verapamil (10 µM) or by PKC inhibition with calphostin-C (250 nM) or Ro-31-8220 (1 µM). In contrast, acute vasoconstriction induced by 10 nM AVP (maximal) was insensitive to blockade of VSCC or PKC inhibition. However, after 30 min, the remaining vasoconstriction induced by 10 nM AVP was partially dependent on PKC activation and almost fully dependent on VSCC. These results suggest that different Ca²⁺ signaling mechanisms contribute to AVP-induced vasoconstriction over different ranges of AVP concentration. Vasoconstrictor actions of AVP, at concentrations of AVP found within the systemic circulation, utilize a Ca²⁺ signaling pathway that is dependent on PKC activation and can be inhibited by Ca²⁺ channel blockers.

pressurized artery; antidiuretic hormone; protein kinase C; vascular smooth muscle; signal transduction

This article has been cited by other articles:

				A. R. Mackie, L. I. Brueggemann, K. K. Henderson, A. J. Shiels, L. L. Cribbs, K. E. Scrogin, and K. L. Byron Vascular KCNQ Potassium Channels as Novel Targets for the Control of Mesenteric Artery Constriction by Vasopressin, Based on Studies in Single Cells, Pressurized Arteries, and in Vivo Measurements of Mesenteric Vascular Resistance J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 475 - 483. [Abstract] [Full Text] [PDF]