The Effect of Norepinephrine on the Coronary Microcirculation

Abstract

The role of the sympathetic nervous system in the regulation of large coronary artery tone has been well defined. Studies of adrenergic regulation of coronary-resistance vessels have largely been limited to indirect inferences based on flow measurement obtained in vivo. The purpose of the present study was to determine the effects of norepinephrine (NE) on the coronary microcirculation using direct in vitro approaches. Porcine coronary microvessels (80-200 µm in diameter) were pressurized in isolated organ chambers. Diameters were measured using a Halpern microvessel imaging apparatus. After preconstriction with leukotriene D₄, NE caused complete relaxation. Relaxations to NE were inhibited by propranolol. Relaxations to NE were also inhibited by LY83583 (which depletes cGMP) and hemoglobin (which binds endothelium-derived relaxing factor, EDRF). NE caused minimal or no constriction in both preconstricted and nonpreconstricted microvessels even in the presence of hemoglobin and propranolol. In conclusion, NE predominantly dilates porcine coronary microvessels, both by β-adrenoceptor activation and by stimulating release of EDRF. There is minimal α-adrenoceptor-mediated constriction of coronary microvessels.

Cardiac Uptake-1 Inhibition by High Circulating Norepinephrine Levels in Patients with Pheochromocytoma

“…This effect is mediated by ␤-2 receptors, and is independent of endothelial function. 21,22 Therefore, decreased cardiac perfusion from coronary artery disease or norepinephrine-mediated vasoconstriction seem unlikely explanations for diminished left ventricular 6-[ 18 F]fluorodopamine-derived radioactivity in patients with high plasma norepinephrine levels.…”

The Role of Nitric Oxide in the Coronary Vasoconstriction Caused by Growth Hormone in Anaesthetized Pigs

“…In the pig heart, the enzyme responsible for the formation of endothelium-derived relaxing factor, nitric oxide synthase, has been shown to be present mainly in the endothelium of the coronary vessels (Ursell & Mayes, 1993). Also, the coronary microvessels of the pig can be dilated both by â-adrenergic activation and by stimulation of nitric oxide release, with only a little effect attributable to á-adrenergic receptor activation (Quillen et al 1992). It is also possible to suggest a clinical implication of the present findings.…”

“…Other reports have indicated that the release of nitric oxide from the endothelium can modulate or mediate â-adrenergic vasodilatory effects in the coronary and peripheral vasculature (e.g. Quillen et al 1992;Parent et al 1993;DiCarlo et al 1995;Persson, 1996), thus raising the possibility that endothelial nitric oxide may be involved in the growth hormone-induced coronary vasoconstriction which is attributed to inhibiting âµ_adrenergic coronary vasodilatory effects. The present investigation in anaesthetized pigs was planned to establish the role of nitric oxide in the vasoconstrictive effect of growth hormone which has been related to inhibiting âµ_adrenergic coronary vasodilatory effects.…”

Estrogen Replacement Increases β-Adrenoceptor-Mediated Relaxation of Rat Mesenteric Arteries

“…ß-Adrenoceptors are present on both smooth-muscle [23,24] and endothelial cells [25,26], and recent reports suggest that the activation of these receptors stimulates the release of nitric oxide through a novel transducing pathway [27], The functional role of ß-adrenoceptors and their contribution to the endothelial modulation of vascu lar tone is still controversial, however, and ß-adrenoceptor-mediated relaxation has been reported both as endo thelial-independent [28,29] and as endothelial-dependent [30,31].…”