Mechanism of vasopressin-induced contraction of renal medullary interstitial cells.
OBJECTIVE
Previous studies have identified a contractile function for renomedullary interstitial cells (RMIC). Such studies focused on the mechanism of endothelin-1-induced RMIC contraction; however, vasopressin (AVP) was also noted to contract RMIC. Since AVP-induced RMIC contraction may be relevant to the medullary effects of AVP on urinary concentration, these initial observations have been extended to examination of the mechanism of AVP-induced RMIC contraction.


METHODS
Cultured rat RMIC were exposed to AVP and other agents, and examined using video microscopy.


RESULTS
AVP caused a slowly developing and dose-dependent reduction in RMIC surface area. AVP-induced RMIC contraction was abolished by blockade of V1, but not V2, receptors. Nifedipine and nickel reduced AVP-stimulated RMIC contraction, indicating that this effect is dependent upon dihydropyridine-sensitive calcium channels. H7, a protein kinase C inhibitor, completely abrogated AVP action, while the nitric oxide synthase inhibitor, NMMA, had no effect. Indomethacin enhanced AVP-induced RMIC contraction, and addition of PGE2 together with indomethacin reduced AVP action.


CONCLUSIONS
These data indicate that AVP potently contracts RMIC via V1 receptor stimulation of PKC and intracellular calcium accumulation, and that AVP-stimulated prostaglandin production downregulates the contractile effect of AVP on RMIC. AVP modulation of RMIC contraction may be involved in the regulation of urinary concentration.
Department of Veterans Affairs Medical Center, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Alisa K
AK
Hughes
Donald E
DE
Kohan
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007425:Intracellular Membranes / Q000378:metabolism; D007679:Kidney Medulla / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011453:Prostaglandins / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000502:physiology
D020746:Calcium Channels, L-Type; D011453:Prostaglandins; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D011493:Protein Kinase C; D002118:Calcium