Smooth muscle hyperpolarization and relaxation to catecholamines in the rat mesenteric artery

Christopher Garland, Polina Iarova, Kathryn Yuill, Kim Dora
University of Bath, Bath, United Kingdom

Although β2-adrenoceptors were thought to be effectively the only subtype of β2-adrenoceptor in the vasculature, it is now clear that β1-adrenoceptors are present in many vessels, including rat small resistance arteries (Briones et al, 2005). This raises the possibility that noradrenaline may have the ability to stimulate vasodilatation under some circumstances. Although it is known that β-adrenoceptor stimulation evokes both smooth muscle hyperpolarization and relaxation in this artery (Gallagher & Garland, 2004) it is not known if, as mixed α/β agonists, noradrenaline and adrenaline can stimulate a similar response.

Male Wistar rats (200-250g) were killed by cervical dislocation and exsanguination (Animals (Scientific Procedures) Act 1986, schedule 1). A 2 mm segment of mesenteric artery was dissected and mounted in a Mulvany-Halpern myograph in oxygenated (95%O2/5%CO2) Krebs buffer or in a pressure myograph (70 mmHg in MOPS) and maintained at 37°C. Endothelium-intact vessels relaxing >90% to 3μM ACh in phenylephrine (1-3μM) constricted arteries were used. NO synthase was inhibited with 100μM L-NAME. Measurement of smooth muscle membrane potential was made with sharp glass microelectrodes (resistance 50-100MΩ)

10nM-3μM noradrenaline progressively depolarized the smooth muscle to a maximum of 17.7±2.6 mV, from a resting potential of -54.2±2.6 mV (n=8), and with a pEC50 of 6.6±0.2. Depolarization was associated with maximum contraction of 12.1±1.1 mN. Qualitatively similar data were obtained with adrenaline, pEC50 7.0±0.1 (n=4). Depolarization and contraction was abolished in the presence of the α-adrenoceptor antagonist, prazosin (1μM), and now both noradrenaline and adrenaline each evoked membrane hyperpolarization of 15.3±2.0 mV and 12.9±2.6 mV (n=7 in each case). The pEC50 values with prazosin present were 5.9±0.1 for noradrenaline and 6.4±0.2 for adrenaline. In the presence of ongoing contraction to U46619, both catecholamines stimulated smooth muscle relaxation.

In isolated mesenteric arteries, both noradrenaline and adrenaline can evoke β-adrenoceptor mediated hyperpolarization and relaxation but this ability is masked in isolated vessels by a predominant α-adrenoceptor effect, expressed as depolarization and contraction. These data raise the possibility that in some situations in vivo noradrenaline may cause or contribute to vasodilatation

Supported by the Wellcome Trust

Briones et al (2005) Br.J.Pharmacol.146: 679-691
Gallagher & Garland (2004) http://www.pA2online.org/vol2issue2abst092P.html