Effects of angiotensin II, arginine vasopressin and tromboxane A2 in renal vascular bed: role of rho-kinase

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2003-09, Vol.18 (9), p.1764-1769
• Main Authors: Cavarape, Alessandro, Bauer, Johannes, Bartoli, Ettore, Endlich, Karlhans, Parekh, Niranjan
• Format: Article
• Language: English
• Subjects: Angiotensin II - pharmacology; Animals; Arginine Vasopressin - pharmacology; Biological and medical sciences; Female; glomerular blood flow; Hydronephrosis - physiopathology; Intracellular Signaling Peptides and Proteins; Kidney - blood supply; Kidney - drug effects; Medical sciences; Models, Animal; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Protein-Serine-Threonine Kinases - physiology; Rats; Rats, Wistar; Renal Circulation - drug effects; Renal failure; renal haemodynamics; rho-Associated Kinases; Signal Transduction - physiology; split hydronephrotic kidney; Thromboxane A2 - pharmacology; Vasoconstriction - physiology; Vasoconstrictor Agents - pharmacology
• ISSN: 0931-0509; 1460-2385; 1460-2385
• DOI: 10.1093/ndt/gfg291

Background. Angiotensin II (Ang II), arginine vasopressin (AVP) and tromboxane A2 (TxA2) are dissimilar vasoconstrictors involved in regulating renal circulation. Whereas Ang II is primarily a physiological modulator, AVP and TxA2 play important roles under pathological conditions. Previously, we have shown variable importance of intracellular Ca2+ and protein kinase C for their mode of action (Ang II > AVP >U-46619), but the cell signalling via rho-associated kinase (ROK) is a common pathway. The aim of this study was to determine their sites of action in the renal vascular bed and the corresponding role of ROK at the microvascular level. Methods. Glomerular blood flow (GBF) and luminal diameter of different vessels (10–70 μm) were measured in the split hydronephrotic kidney of anaesthetized rats. The tissue bath concentration of Ang II, AVP or the TxA2 agonist U-46619 was adjusted to reduce GBF by ∼50%. The measurements were repeated after adding a sub-maximal dose of the ROK inhibitor Y-27632 into the bath. Results. Ang II constricted all vessels significantly, the constriction being least in the proximal segment of the arcuate artery (∼70 μm). Significant constrictions due to AVP were found only in interlobular and arcuate arteries (20–70 μm), but not in the afferent and efferent arterioles. U-46619 constricted only the arcuate artery (≥50 μm). Y-27632 (10–4 M) dilated all vessels significantly and increased GBF by 65%. Thereafter, effects of all agonists were severely attenuated. Control reductions in GBF could be obtained at higher concentrations of AVP (10-fold) and U-46619 (5-fold) and a lesser GBF reduction with Ang II (100-fold) without changes in the respective patterns of vascular constriction. Conclusions. Our data indicate that the agonists, in the order Ang II, AVP and TxA2, constrict larger vessels within the renal vascular tree via activation of ROK. Therefore, ROK inhibitors may provide a therapeutic tool to antagonize pathological vasospasm of conduit vessels, which are resistant to other vasodilators.