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

Connexin43 (Cx43) is a major gap junction protein present in the Fischer-34 4 rat aorta. Previous studies have identified conditions under which select ive disruption of intercellular communication with heptanol caused a signif icant, readily reversible and time-dependent diminution in the magnitude of alpha(1)-adrenergic contractions in isolated rat aorta. These observations have indentified a significant role for gap junctions in modulating vascul ar smooth muscle tone. The goal of these steady-state studies was to utiliz e isolated rat aortic rings to further evaluate the contribution of interce llular junctions to contractions elicited by cellular activation in respons e to several other vascular spasmogens. The effects of heptanol were examin ed (0.2-2.0 mM) on equivalent submaximal (approximate to 75% of the phenyle phrine maximum) aortic contractions elicited by 5-hydroxykyptamine (5-HT; 1 -2 mu M), prostaglandin F-2 alpha (PGF(2 alpha); 1 mu M) and endothelin-1 ( ET-1; 20 nM). Statistical analysis revealed that 200 mu M and 500 mu M hept anol diminished the maximal amplitude of the steady-state contractile respo nses 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), a nd for PGF(2 alpha) 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 mu M and 500 mu M 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 mu M heptanol (N = 17 rings), and 70 +/- 6.0% in the presence of 500 m u M 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 addition al effect. In rat aorta then, junctional modulation of tissue contractility appears to be agonist-dependent.