Urocortin relaxes rat tail arteries by a PKA‐mediated reduction of the sensitivity of the contractile apparatus for calcium

Abstract

1 Urocortin is an endogenous vasodilator although the mechanism of vasorelaxation is not completely understood. The hypothesis that an alteration of smooth muscle calcium concentration is involved was tested using isometric tension recording and calcium¯uorimetry. The relationship between contraction and intracellular calcium was also estimated. 2 Urocortin produced a concentration dependent relaxation (pD 2 8.59+0.06, n=6) of vessels precontracted with a physiological salt solution containing 42 mM KCl (42 mM K-PSS). 3 Removal of the endothelium did not alter the e ect of urocortin, pD 2 was 8.49+0.11, n=5. 4 Corticotropin-releasing factor relaxed 42 mM K-PSS pre-contracted vessels with less potency compared to urocortin (pD 2 6.99+0.28, n=5). 5 Urocortin at 100 nM relaxed vessels pre-contracted with 42 mM K-PSS by 59.6+4.6% (n=8) and vessels pre-contracted with 500 nM noradrenaline by 25.2+6.8% (n=6). Both e ects were not accompanied by a change in the intracellular calcium concentration. 6 Urocortin at 100 nM produced a signi®cant rightward shift of 0.33+0.07 units of normalized intracellular calcium (n=5) of the relationship between tension and intracellular calcium. 7 The urocortin-induced relaxation was considerably reduced in the presence of 0.3 mM Rp-8-CPTcAMPS, a cyclic AMP-dependent protein kinase (PKA) inhibitor. 8 The PKA-activator Sp-5,6-DCl-cBIMPS relaxed 42 mM K-PSS pre-contracted vessels (pD 2 4.98+0.07, n=6). Sp-5,6-DCl-cBIMPS at 0.1 mM relaxed vessels by 85.3+2.5% (n=5), but did not change the intracellular calcium concentration. 9 In conclusion, the data show that urocortin is a potent, endothelium-independent dilator of rat tail arteries and suggest that this e ect is mediated by PKA causing a reduction of the sensitivity of the contractile apparatus for calcium.

Role of Corticotropin-Releasing Factor Receptor Type 2β in Urocortin-Induced Vasodilation of Rat Aortas

“…It has been reported that urocortin is a potent, endothelium-independent dilator of WKY rat tail arteries, because denudation did not affect the vasodilation effect of urocortin (14). However, the urocortin receptor CRF-R2b has been reported to be found in both vascular endothelial cells and smooth muscle cells (15), which was also confirmed in this report.…”

“…A cyclic AMP-dependent protein kinase inhibitor, Rp-8-CPT-cAMPS, significantly reduced the vasodilation, suggesting an increase in cyclic AMP concentration evoked by urocortin (14). Urocortin-induced vasodilation of isolated thoracic aorta without endothelium was significantly inhibited by SQ22536, an adenylyl cyclase inhibitor.…”

Urocortin Induces Endothelium-Dependent Vasodilatation and Hyperpolarization of Rat Mesenteric Arteries by Activating Ca2+-Activated K+ Channels

“…Studies on the isolated preparations have shown that urocortin causes relaxation of rat arteries and veins (Schilling et al 1998;Lubomirov et al 2001;Terui et al 2001), and human placenta (Leitch et al 1998) and saphe-artery and the vascular bed flushed with heparinized Krebs-Henseleit solution. The mesenteric vascular bed was then dissected away from the connecting tissues and transferred to a warmed chamber where it was perfused with gassed (95% O 2 + 5% CO 2 ) Krebs-Henseleit solution (mM composition: NaCl 119, KCl 4.6, CaCl 2 1.5, MgCl 2 1.2, NaHCO 3 15, NaHPO 4 1.2 and glucose 11) maintained at 37°C with a constant flow rate of 6.5 ml/ min using a peristaltic pump (Buchler Instruments, USA).…”

“…It has been demonstrated that urocortin-induced relaxation is both endotheliumdependent and -independent in the coroner artery. Endothelium-dependent component of the relaxation is contributed by nitric oxide (NO) (Huang et al 2002), while the other component is mediated by intracellular cAMP (Huang et al 2003), which was also demonstrated in rat tail arteries (Lubomirov et al 2001). On the other hand, in the isolated perfused rat heart, urocortin-induced coronary vasodilatation may partly depend on prostaglandins (Terui et al 2001).…”

Ο Ρόλος Των Νευροπεπτιδίων Της Οικογένειας Του Εκλυτικού Παράγοντα Της Κορτικοτροπίνης Και Των Ουροκορτινών Στην Αλληλεπίδραση Των Μακροφάγων Με Το Αγγειακό Ενδοθήλιο

“…H αναστολή της δράσης της CRH µετά τον εκλεκτικό αποκλεισµό των CRH υποδοχέων υποδηλώνει συµµετοχή και των δύο. Οι UCNs είναι γενικά αποδεκτές ως καρδιοπροστατευτικοί παράγοντες [247][248][249][250][251][252][253][254][255][256][257][258][259][260][261].…”