title: Effects of angiotensin II, arginine vasopressin and tromboxane A2 in renal vascular bed: role of rho-kinase.
abstract: BACKGROUND
  Angiotensin II (Ang II), arginine vasopressin (AVP) and tromboxane A(2) (TxA(2)) are dissimilar vasoconstrictors involved in regulating renal circulation. Whereas Ang II is primarily a physiological modulator, AVP and TxA(2) play important roles under pathological conditions. Previously, we have shown variable importance of intracellular Ca(2+) 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 micro m) were measured in the split hydronephrotic kidney of anaesthetized rats. The tissue bath concentration of Ang II, AVP or the TxA(2) agonist U-46619 was adjusted to reduce GBF by approximately 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 ( approximately 70 micro m). Significant constrictions due to AVP were found only in interlobular and arcuate arteries (20-70 micro m), but not in the afferent and efferent arterioles. U-46619 constricted only the arcuate artery (> or = 50 micro m). 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 TxA(2), 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.
authors.affiliation: Department of Experimental and Clinical Pathology and Medicine, Chair of Internal Medicine, University of Udine, Udine, Italy. alessandro.cavarape@dpmsc.uniud.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cavarape
authors.forename: Johannes
authors.initials: J
authors.lastname: Bauer
authors.forename: Ettore
authors.initials: E
authors.lastname: Bartoli
authors.forename: Karlhans
authors.initials: K
authors.lastname: Endlich
authors.forename: Niranjan
authors.initials: N
authors.lastname: Parekh
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D005260:Female; D006869:Hydronephrosis / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D023421:Models, Animal; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D015398:Signal Transduction / Q000502:physiology; D013928:Thromboxane A2 / Q000494:pharmacology*; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D054460:rho-Associated Kinases
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; D013928:Thromboxane A2; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases