Nephrol Dial Transplant (2003) 18: 1764-1769
© 2003 European Renal Association-European Dialysis and Transplant Association
Effects of angiotensin II, arginine vasopressin and tromboxane A2 in renal vascular bed: role of rho-kinase
1 Department of Experimental and Clinical Pathology and Medicine, Chair of Internal Medicine, University of Udine, Udine, 2 Department of Medical Science, Chair of Internal Medicine, University of Piemonte Orientale ‘A. Avogadro’, Novara, Italy, 3 Department of Neonatology, 4 Department of Cell Biology and Anatomy and 5 Department of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany
Correspondence and offprint requests to: Alessandro Cavarape, MD, Department of Experimental and Clinical Pathology and Medicine (DPMSC), Chair of Internal Medicine, Piazza S. Maria della Misericordia, 1, I-33100 Udine, Italy. Email: alessandro.cavarape{at}dpmsc.uniud.it
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.
Keywords: glomerular blood flow; renal haemodynamics; split hydronephrotic kidney
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Ponnuchamy and R. A. Khalil Cellular mediators of renal vascular dysfunction in hypertension Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R1001 - R1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W. Inscho, A. K. Cook, R. C. Webb, and L.-M. Jin Rho-kinase inhibition reduces pressure-mediated autoregulatory adjustments in afferent arteriolar diameter Am J Physiol Renal Physiol, March 1, 2009; 296(3): F590 - F597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Schluter, A. C. Steinbach, A. Steffen, R. Rettig, and O. Grisk Apocynin-induced vasodilation involves Rho kinase inhibition but not NADPH oxidase inhibition Cardiovasc Res, November 1, 2008; 80(2): 271 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Thachil The implications of aspirin resistance in renal failure NDT Plus, June 1, 2008; 1(3): 192 - 193. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Bussemaker, F. Pistrosch, S. Forster, K. Herbrig, P. Gross, J. Passauer, and R. P. Brandes Rho kinase contributes to basal vascular tone in humans: role of endothelium-derived nitric oxide Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H541 - H547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hayashi, S. Wakino, N. Sugano, Y. Ozawa, K. Homma, and T. Saruta Ca2+ Channel Subtypes and Pharmacology in the Kidney Circ. Res., February 16, 2007; 100(3): 342 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. Windt, A. Tahara, A. C. Kluppel, D. de Zeeuw, R. H Henning, and R. P. van Dokkum Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy Journal of Renin-Angiotensin-Aldosterone System, December 1, 2006; 7(4): 217 - 224. [Abstract] [PDF]
|
|
|
|
|
|
J. Song, C. K. Kost Jr., and D. S. Martin Androgens potentiate renal vascular responses to angiotensin II via amplification of the Rho kinase signaling pathway Cardiovasc Res, December 1, 2006; 72(3): 456 - 463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Winaver, E. Ovcharenko, I. Rubinstein, K. Gurbanov, P. Pollesello, B. Bishara, A. Hoffman, and Z. Abassi Involvement of Rho kinase pathway in the mechanism of renal vasoconstriction and cardiac hypertrophy in rats with experimental heart failure Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H2007 - H2014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shi, X. Wang, K. H. Chon, and W. A. Cupples Tubuloglomerular feedback-dependent modulation of renal myogenic autoregulation by nitric oxide Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R982 - R991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. H. Hansen, O. B. Vagnes, and B. M. Iversen Enhanced response to AVP in the interlobular artery from the spontaneously hypertensive rat Am J Physiol Renal Physiol, May 1, 2005; 288(5): F1023 - F1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bellomo, C. May, L. Wan, W. L. Jackson Jr., G. A. Heresi, F. J. Haddy, R. W. Schrier, and W. Wang Acute Renal Failure and Sepsis N. Engl. J. Med., November 25, 2004; 351(22): 2347 - 2349. [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Ryan, S. P. Didion, S. Mathur, F. M. Faraci, and C. D. Sigmund Angiotensin II-Induced Vascular Dysfunction Is Mediated by the AT1A Receptor in Mice Hypertension, May 1, 2004; 43(5): 1074 - 1079. [Abstract] [Full Text] [PDF]
|
|