Urotensin II acutely increases myocardial length and distensibility: potential implications for diastolic function and ventricular remodeling

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Ana Patricia Fontes Sousa (Author) Other; Carmen Bras Silva (Author) FCNAUP; Ana Luisa Pires (Author) Other; Daniela Monteiro Sousa (Author) Other; Adelino F Leite Moreira (Author) FMUP

Journal

Title: Naunyn-Schmiedeberg's Archives of Pharmacology

Vol. 376

Pages: 107-115

ISSN: 0028-1298

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 14 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-00H-31K

DOI: 10.1007/s00210-007-0180-8

Abstract (EN): Urotensin II (U-II) is a cyclic peptide that may be involved in cardiovascular dysfunction. In the present study, the acute effects of U-II on diastolic properties of the myocardium were investigated. Increasing concentrations of U-II (10(-8) to 10(-6) M) were added to rabbit papillary muscles in the absence (n = 15) or presence of: (1) damaged endocardial endothelium (EE; n = 9); (2) U-II receptor antagonist, urantide (10(-5) M; n = 7); (3) nitric oxide (NO) synthase inhibitor, NG-Nitro-L-Arginine (10(-5) M; n = 9); (4) cyclooxygenase inhibitor, indomethacin (10(-5) M; n = 8); (5) NO synthase and cyclooxygenase inhibitors, NG-Nitro-L-Arginine (10(-5) M) and indomethacin (10(-5) M), respectively, (n = 8); or (6) protein kinase C (PKC) inhibitor, chelerythrine (10(-5) M; n = 9). Passive length-tension relations were constructed before and after a single concentration of U-II (10(-6) M; n = 3). U-II concentration dependently decreased inotropy and increased resting muscle length (RL). At 10(-6) M, active tension decreased 13.8 +/- 5.4%, and RL increased to 1.007 +/- 0.001 L/L-max. Correcting RL to its initial value resulted in an 18.1 +/- 3.0% decrease in resting tension, indicating decreased muscle stiffness, which was also suggested by the down and rightward shift of the passive length-tension relation. This effect remained unaffected by EE damage and PKC inhibition. In contrast, the presence of urantide and NO inhibition abolished the effects of U-II on myocardial stiffness, while cyclooxygenase inhibition significantly attenuated them. U-II decreases myocardial stiffness, an effect that is mediated by the urotensin-II receptor, NO, and prostaglandins. This represents a novel mechanism of acute neurohumoral modulation of diastolic function, suggesting that U-II is an important regulator of cardiac filling.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9