Mechanism of Vasopressin-Induced Contraction of Renal Medullary Interstitial Cells

Abstract

Background/Aims: 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. Conclusion: 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.