title: Urotensin II-induced increase in myocardial distensibility is modulated by angiotensin II and endothelin-1.
abstract: Endogenous regulators, such as angiotensin-II (AngII), endothelin-1 (ET-1) and urotensin-II (U-II) are released from various cell types and their plasma levels are elevated in several cardiovascular diseases. The present study evaluated a potential crosstalk between these systems by investigating if the myocardial effects of U-II are modulated by AngII or ET-1. Effects of U-II (10(-8), 10(-7), 10(-6) M) were tested in rabbit papillary muscles in the absence and in the presence of losartan (selective AT(1) receptor antagonist), PD-145065 (nonselective ET-1 receptors antagonist), losartan plus PD-145065, AngII or ET-1. U-II promoted concentration-dependent negative inotropic and lusitropic effects that were abolished in all experimental conditions. Also, U-II increased resting muscle length up to 1.008+/-0.002 L/L(max). Correcting it to its initial value resulted in a 19.5+/-3.5 % decrease of resting tension, indicating increased muscle distensibility. This effect on muscle length was completely abolished in the presence of losartan and significantly attenuated by PD-145065 or losartan plus PD-145065. This effect was increased in the presence of AngII, resulting in a 27.5+/-3.9 % decrease of resting tension, but was unaffected by the presence of ET-1. This study demonstrated an interaction of the U-II system with the AngII and ET-1 systems in terms of regulation of systolic and diastolic function.
authors.affiliation: Department of Physiology, Alameda Professor Hernâni Monteiro, Porto 4200-319, Portugal.
authors.forename: A P
authors.initials: AP
authors.lastname: Fontes-Sousa
authors.forename: A L
authors.initials: AL
authors.lastname: Pires
authors.forename: V F
authors.initials: VF
authors.lastname: Monteiro-Cardoso
authors.forename: A F
authors.initials: AF
authors.lastname: Leite-Moreira
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism*; D006321:Heart / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D014579:Urotensins / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D014579:Urotensins; D000804:Angiotensin II; C029677:urotensin II