Endothelium-Dependent, Vasopressin-Induced Contractions in Rabbit Renal Arteries

Objectives: To identify and quantify the stimulatory and inhibitory activity of endothelial factors on Arginine vasopressin (AVP)-induced contractions. Methods: In a standard organ bath set-up for isometric force recording, rabbit isolated renal artery rings were exposed to cumulative concentrations of AVP. Experiments were performed in the presence or absence of functional endothelium, or in the presence of N-Nitro-L-Arginine 10 μM (L-NNA) (NO-synthase inhibitor). Results: Arginine vasopressin induced a maximal contractile response of 6.5 ± 0.1 mN in vessels with and 6.3 ± 0.3 mN in vessels without endothelium. The preincubation with L-NNA resulted in an enhanced response to AVP of 12.6 ± 0.8 mN (P < 0.05). The augmentation of the AVP induced contractile response by NOS inhibition, which was not seen in preparations after the removal of the endothelium, suggests an endothelium dependent factor that is co-released with NO. The unknown nature of this endothelium dependent contractile factor was not influenced by indomethacin 100 μM (cyclooxygenase inhibitor), meclofenamic acid 20 μM (cyclooxygenase and lipoxygenase inhibitor), or bosentan 100 μM (endothelin antagonist). Charybdotoxin 0.1 μM (inhibitor of Ca 2+-activated K+ channels) specifically increased the contractile force in preparations with and without endothelium, or in the presence of L-NNA to 11.2 ± 0.4 mN, 14.0 ± 0.8 mN, and 19.0 ± 0.8 mN, respectively (P < 0.05 compared with the experiments without charybdotoxin). SR 49059 (vasopressin 1 receptor (V1) antagonist) antagonized the effects of AVP, whereas SR 121463 B (V2 antagonist) was ineffective. In contrast to the results obtained with AVP, desmopressin (V2 agonist) showed no effect. Conclusion: The completely V1 dependent AVP-induced contraction is partly inhibited by the stimulated release of NO. This was only demonstrable in endothelium intact vessels in the presence of L-NNA and not after removal of the endothelium. This strongly suggests the involvement of an unknown endothelium V1 receptor dependent contractile factor that is not influenced by inhibition of the prostaglandin, lipoxygenase, or endothelin pathway, or by blockade of the V2 receptor.