Gap junctions in isolated rat aorta: evidence for contractile responses that exhibit a differential dependence on intercellular communication

Abstract

Connexin43 (Cx43) is a major gap junction protein present in the Fischer-344 rat aorta. Previous studies have identified conditions under which selective disruption of intercellular communication with heptanol caused a significant, readily reversible and time-dependent diminution in the magnitude of a 1 -adrenergic contractions in isolated rat aorta. These observations have indentified a significant role for gap junctions in modulating vascular smooth muscle tone. The goal of these steady-state studies was to utilize isolated rat aortic rings to further evaluate the contribution of intercellular junctions to contractions elicited by cellular activation in response to several other vascular spasmogens. The effects of heptanol were examined (0.2-2.0 mM) on equivalent submaximal (»75% of the phenylephrine maximum) aortic contractions elicited by 5-hydroxytryptamine (5-HT; 1-2 µM), prostaglandin F 2= (PGF 2= ; 1 µM) and endothelin-1 (ET-1; 20 nM). Statistical analysis revealed that 200 µM and 500 µM heptanol diminished the maximal amplitude of the steady-state contractile responses for 5-HT from a control response of 75 ± 6% (N = 26 rings) to 57 ± 7% (N = 26 rings) and 34.9 ± 6% (N = 13 rings), respectively (P<0.05), and for PGF 2= from a control response of 75 ± 10% (N = 16 rings) to 52 ± 8% (N = 19 rings) and 25.9 ± 6% (N = 18 rings), respectively (P<0.05). In contrast, 200 µM and 500 µM heptanol had no detectable effect on the magnitude of ET-1-induced contractile responses, which were 76 ± 5.0% for the control response (N = 38 rings), 59 ± 6.0% in the presence of 200 µM heptanol (N = 17 rings), and 70 ± 6.0% in the presence of 500 µM heptanol (N = 23 rings) (P<0.13). Increasing the heptanol concentration to 1 mM was associated with a significant decrease in the magnitude of the steady-state ET-1-induced contractile response to 32 ± 5% (21 rings; P<0.01); further increasing the heptanol concentration to 2 mM had no additional effect. In rat aorta then, junctional modulation of tissue contractility appears to be agonist-dependent.

Replacement of connexin 43 by connexin 32 in a knock‐in mice model attenuates aortic endothelium‐derived hyperpolarizing factor‐mediated relaxation

“…1997), suggesting that smooth muscle gap junctions are essential for its action. Similar effects were observed with heptanol on 5‐hydroxytryptamine‐ and prostaglandin F 2α ‐induced contractions in rat aortic rings, but not on contractility in response to endothelin‐1 (Christ & Brink, 2000).…”

“…Moreover, vascular gap junctions have been described to modulate both contraction and relaxation responses differentially in larger blood vessels (Chaytor et al . 1997, 1998; Christ & Brink, 2000). Synthetic Cx43‐mimetic peptides have been shown to abolish the rhythmic contractile activity induced by phenylephrine in endothelium‐denuded rabbit mesenteric arteries (Chaytor et al .…”

Coordination of Mesangial Cell Contraction by Gap Junction–Mediated Intercellular Ca2+ Wave

“…We therefore tried to elucidate the physiologic relevance of this wave in MC. For this purpose, we have chosen the contraction of MC as a parameter for investigation on the basis of the following considerations: (1) the coordinated contraction of MC is critical for the regulation of glomerular hemodynamics (41); (2) the critical role of Ca 2ϩ in the regulation of MC contraction is well established (13,41); (3) it is well known that synchronized contraction of heart myocytes depends on the GJ communication (42); and (4) the importance of GJ in the regulation of integrated responses of smooth muscle cells in vascular contraction and relaxation are now being recognized (43)(44)(45). To elicit a Ca 2ϩ wave in MC, we also employed injection of IP 3 as an alternative to mechanical stimulation.…”

Disruption of smooth muscle gap junctions attenuates myogenic vasoconstriction of mesenteric resistance arteries

“…For example, inhibition of intercellular communication attenuates conducted vasodilatory and vasoconstrictor responses (15,17,18,39,45) as well as endothelium-derived hyperpolarizing factor-type vasodilation (4) in some vascular beds. In addition, disruption of gap junctions impairs both pressure (32) and agonist-induced (6,8) vasoconstrictor responses. These later findings imply that synchronization of the contractile state of VSM cells within the vessel wall contributes to typical constrictor function by allowing coordinated generation of force (7).…”