Urotensin II alters vascular reactivity in animals subjected to volume overload.
Congestive heart failure (CHF) alters vascular reactivity and up regulates in urotensin II (UTII), a potent vasoactive peptide. The aim of this study was to investigate the interaction between CHF and UTII in altering vascular reactivity in a rat model of volume overload heart failure. Animals were divided into 4 groups: control, UTII infused (UTII), volume overload only (VO) or volume overload+UTII (VO+UTII). Volume overload was established by the formation of an aortocaval fistula. Following fistula formation animals were administered UTII at a rate of 300 pmol/kg/h for 4 weeks subcutaneously with mini-osmotic pumps. Thoracic aorta rings, with/without endothelium, were subjected to cumulative dose-responses to phenylephrine, sodium nitroprusside (SNP), acetylcholine (ACH), UTII, and the Rho-kinase inhibitor HA-1077. Aortas from VO animals exhibited increased sensitivity to phenylephrine and UTII with a decreased relaxation response to ACH and HA-1077. Aortas from animals subjected to chronic UTII with volume overload (VO + UTII) retained their sensitivity to phenylephrine and UTII while they improved their relaxation to HA-1077 but not ACH. The constrictive response to UTII was dose-dependent and augmented at concentrations <0.01 μM in VO animals. The changes in vascular reactivity paralleled an elevation of both the UTII and α(1A)-adrenergic receptor while the Rho and Rho-kinase signalling proteins were diminished. We found that volume overload increased sensitivity to the vasoconstrictor agents that was inversely related to changes in the Rho-kinase expression. The addition of UTII with VO reversed the constrictive vascular response through alterations in the Rho-kinase signalling pathway.
Harris
Gregory S
GS
Department of Physiology, Brody School of Medicine at East Carolina University, 600 Moye Blvd Brody Building 6N98, Greenville, NC 27834, USA.
Lust
Robert M
RM
Katwa
Laxmansa C
LC
Wingard
Christopher J
CJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects; D002306:Cardiac Volume; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D008297:Male; D023421:Models, Animal; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D014579:Urotensins / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014684:Venae Cavae / Q000601:surgery; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C473142:Uts2r protein, rat; D009599:Nitroprusside; D010656:Phenylephrine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C029677:urotensin II; D054460:rho-Associated Kinases; D000109:Acetylcholine; C049347:fasudil