Longer muscle lengths recapitulate force suppression in swine carotid artery

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Abstract
Cyclic nucleotide can relax arterial smooth muscle without reductions in myosin regulatory light chain (MRLC) phosphorylation, a process termed force suppression. Smooth muscle contractile force also depends on tissue length. It is not known how tissue length affects force suppression. Swine carotid artery rings were equilibrated at various lengths (as a fraction of Lo, the optimal length for force development). They were then frozen during contractile activation with or without forskolin-induced relaxation. Frozen tissue homogenates were then analyzed for Ser19-MRLC phosphorylation and Ser16-heat shock protein 20 (HSP20) phosphorylation (HSP20 is the proposed mediator of force suppression). Higher values of MRLC phosphorylation were required to induce a histamine contraction at longer tissue lengths. At 1.4 Lo, the dependence of force on MRLC phosphorylation observed with histamine stimulation alone was shifted to the right, a response similar to that observed during force suppression at 1.0 Lo. The rightward shift in the dependence of force on MRLC phosphorylation seen with histamine stimulation alone at 1.4 Lowas not associated with increased HSP20 phosphorylation. Addition of forskolin to histamine-stimulated tissues at 1.4 Loinduced a relaxation associated with increased HSP20 phosphorylation and reduced MRLC phosphorylation, i.e., there was no additional force suppression. At shorter tissue lengths (0.6 Lo), the dependence of force on MRLC phosphorylation with histamine stimulation alone was steep, a response similar to that observed during normal contractile activation at 1.0 Lo. Addition of forskolin induced force suppression at 0.6 Lo. The sensitivity of swine carotid to the concentration of histamine was greater at longer tissue lengths compared with shorter tissue lengths, suggesting a physiological mechanism to restore optimal tissue length. These data suggest that longer tissue lengths induced a force suppression-like state that was 1) not additive with forskolin and 2) not associated with HSP20 phosphorylation. Further research is required to determine this length-dependent mechanism.