Gender-specific K⁺-channel contribution to adenosine-induced relaxation in coronary arterioles

Abstract

Heaps, Cristine L., and Douglas K. Bowles. Gender-specific K ϩ -channel contribution to adenosine-induced relaxation in coronary arterioles. J Appl Physiol 92: 550-558, 2002. First published October 5, 2001 10.1152/ japplphysiol.00566.2001.-We examined the contribution of K ϩ -channel activity on basal tone and adenosine-mediated relaxation of coronary arterioles isolated from sexually mature male and female miniature swine. Arterioles (ϳ100-200 m ID) isolated from the apical region of the heart were cannulated and studied using videodimensional analysis under constant intraluminal pressure. Coronary arterioles from male and female pigs demonstrated similar levels of basal tone and reductions in basal diameter in response to the K ϩ -channel blockers 4-aminopyridine (4-AP; 1 mM), tetraethylammonium (1 mM), and glibenclamide (Glib; 10 M), with 4-AP producing significantly greater constriction than tetraethylammonium or Glib. After endothelin-induced preconstriction, relaxation responses to adenosine were not significantly different between coronary arterioles of male and female pigs. Inhibition of 4-AP-sensitive channels significantly impaired adenosine-mediated relaxation in arterioles from male but not female pigs. However, inhibition of K ϩ channels with iberiotoxin (100 nM) or Glib had no effect on adenosine-induced relaxation in either sex. Results obtained in the presence of nitric oxide synthase inhibition suggest a potential interaction of 4-AP-sensitive channels and nitric oxide at low adenosine concentrations. In conclusion, our data indicate that 4-AP-sensitive channels 1) contribute significantly to basal tone in coronary arterioles of both male and female pigs, 2) contribute to adenosine-mediated relaxation in male but not female pigs, and 3) can contribute to adenosine-induced relaxation independent of nitric oxide production in male pigs. These data are consistent with a significant role for voltage-dependent K ϩ channels in adenosine-mediated relaxation of coronary arterioles from males. potassium channel; smooth muscle; endothelium; nitric oxide synthase; endothelin ADENOSINE IS AN ENDOGENOUS vasodilator that produces vascular smooth muscle relaxation through a variety of mechanisms that act to reduce intracellular Ca 2ϩ levels and decrease Ca 2ϩ sensitivity of the contractile apparatus. K ϩ -channel activation has been identified as an important component of adenosine-mediated relaxation (7,13,19,31). Increased K ϩ -channel activity hyperpolarizes smooth muscle and thereby reduces smooth muscle contraction via reduced Ca 2ϩ entry through voltage-dependent Ca 2ϩ channels.Both Ca 2ϩ -activated K ϩ (K Ca ) channels and ATPsensitive K ϩ (K ATP ) channels have been reported to contribute to adenosine-mediated relaxation in vascular smooth muscle. Price and colleagues (7, 31) have demonstrated significant roles for K Ca channels in both basal tone and adenosine-mediated relaxation in pressurized canine coronary arterioles. In contrast, Kuo and colleagues (13,19) reported that inhibition of K ATP chan...

Hypercholesterolemia abolishes voltage-dependent K+ channel contribution to adenosine-mediated relaxation in porcine coronary arterioles

“…3B) animals. These data confirm our previous report that K v channels contribute significantly to adenosine-induced relaxation in coronary arterioles from male pigs (13). In contrast, hypercholesterolemia abolished the contribution of K v channels to adenosine-mediated relaxation.…”

“…The contribution of KATP channels to whole cell K ϩ current was minimized by inclusion of 2 mM ATP in the pipette solution. These conditions allowed us to isolate K v currents (13,22,30). Cells were initially superfused with PSS containing (in mM): 138 NaCl, 5 KCl, 0.1 CaCl 2, 1 MgCl2, 10 glucose, 20 HEPES, pH 7.4.…”

“…Additional studies have reported reduced K ϩ channel activity in vascular smooth muscle under hypercholesterolemic conditions (10,21,23), which likely contributes to impaired vasodilatory responses of affected arteries. Recent in vitro studies of the coronary microcirculation from our laboratory have provided the first evidence for significant voltage-dependent K ϩ (K v ) channel contribution to adenosine-mediated relaxation in arterioles from control minipigs (13). Taken together, these findings prompted us to test the hypothesis that adenosine-mediated relaxation is significantly impaired in coronary arterioles of hypercholesterolemic animals and is attributable to an impaired adenosine-activation of K v channels.…”

Coronary microvascular reactivity is only partially predicted by atherosclerosis risk factors or coronary artery disease in women evaluated for suspected ischemia: results from the NHLBI Women's Ischemia Syndrome Evaluation (WISE)

“…The vasodilator stimulus is often adenosine (Ado) and a gender-specific contribution to Adoinduced coronary arteriole dilation has been reported. 15 In the Women's Ischemia Syndrome Evaluation (WISE), diminished reactivity was frequent even without obstructive CAD. 1 Myocardial perfusion alterations in response to Ado-induced vasodilation are not infrequent in women without obstructive CAD 16 and do not necessarily correlate with endothelial dysfunction.…”

Mechanisms involved in the adenosine-induced vasorelaxation to the pig prostatic small arteries

“…Both K ATP and K Ca are involved in adenosine A 2A and A 2B receptors-mediated hyperpolarization, which also leads to NO release in coronary endothelial cells [5]. In addition to these channels, Kv channels are involved in adenosine-mediated relaxation of coronary arterioles from pig males [47]. Kv channels of the of the Kv1.3 family have also been reported in rat prostate epithelial cells, and a significant increase in Kv channel expression, particularly of the Kv1 and Kv2 subfamily members, has been shown to be involved in the proliferation of prostate carcinoma [48,49].…”