| First Author | Haghbin N | Year | 2024 |
| Journal | Sci Rep | Volume | 14 |
| Issue | 1 | Pages | 24940 |
| PubMed ID | 39438518 | Mgi Jnum | J:357417 |
| Mgi Id | MGI:7763318 | Doi | 10.1038/s41598-024-75838-8 |
| Citation | Haghbin N, et al. (2024) Functional bias of contractile control in mouse resistance arteries. Sci Rep 14(1):24940 |
| abstractText | Constrictor agonists set arterial tone through two coupling processes, one tied to (electromechanical), the other independent (pharmacomechanical) of, membrane potential (V(M)). This dual arrangement raises an intriguing question: is the contribution of each mechanism (1) fixed and proportionate, or (2) variable and functionally biased. Examination began in mouse mesenteric arteries with a vasomotor assessment to a classic G(q/11) (phenylephrine) or G(q/11)/G(12/13) (U46619) agonist, in the absence and presence of nifedipine, to separate among the two coupling mechanisms. Each constrictor elicited a concentration response curve that was attenuated and rightward shifted by nifedipine, findings consistent with functional bias. Electromechanical coupling preceded pharmacomechanical, the latter's importance rising with agonist concentration. In this regard, ensuing contractile and phosphorylation (CPI-17 & MYPT1 (T-855 & T-697)) measures revealed phenylephrine-induced pharmacomechanical coupling was tied to protein kinase C (PKC) activity, while that enabled by U46619 to PKC and Rho-kinase. A complete switch to pharmacomechanical coupling arose when agonist superfusion was replaced by pipet application to a small portion of artery. This switch was predicted, a priori, by a computer model of electromechanical control and supported by additional measures of V(M) and cytosolic Ca(2+). We conclude that the coupling mechanisms driving agonist-induced constriction are variable and functionally biased, their relative importance set in accordance with agonist concentration and manner of application. These findings have important implications to hemodynamic control in health and disease, including hypertension and arterial vasospasm. |
