Stefan Mellander

Effects of selective ETB-receptor stimulation on arterial, venous and capillary functions in cat skeletal muscle

1 This paper describes, in quantitative terms, the in vivo effects of two selective ETB‐receptor agonists (IRL 1620 and BQ 3020) on vascular resistance (tone) in the following consecutive sections of the vascular bed of sympathectomized cat skeletal muscle: large‐bore arterial resistance vessels (> 25 μm), small arterioles (< 25 μm) and the veins. The effects on capillary pressure and transcapillary fluid exchange were also recorded. 2 Both IRL 1620 and BQ 3020, infused i.a. to the muscle preparation, evoked an initial transient dilator response followed by a moderate dose‐dependent constrictor response, both being preferentially confined to the small arterioles. The dilator response was associated with a transient increase, and the constrictor response with a sustained decrease, in capillary pressure, the latter causing net transcapillary fluid absorption. The capillary filtration coefficient decreased during the constrictor response, indicating constriction of terminal arterioles/precapillary sphincters. 3 The vascular responses to the ETB‐receptor agonists were unaffected by blockade of endothelium‐derived nitric oxide (NG‐nitro‐l‐arginine methyl ester) and by selective ETA‐receptor blockade (FR139317). However, blockade of prostacyclin production with indomethacin decreased the amplitude of the dilator response, and decreased the time required to reach a steady‐state vasoconstrictor response to the ETB‐receptor agonists. 4 The effect of ETB‐receptor stimulation on vascular tone was also evaluated in vitro on the cat femoral artery and vein. IRL 1620 had no effect on the femoral artery but caused a weak dose‐dependent relaxation in the femoral vein. This large vein relaxation response seemed to be mediated by endothelium‐derived nitric oxide and not by prostacyclin. 5 It may be concluded that ETB‐receptor stimulation is responsible for the dilator response, and can contribute to the constrictor response, elicited by endothelins in cat skeletal muscle in vivo.

On the control of capillary fluid transfer by precapillary and postcapillary vascular adjustments: A brief review with special emphasis on myogenic mechanisms

Abstract This paper summarizes some concepts of the internal fluid balance in the body as it is governed by circulatory control systems via specific influences on net transcapillary and transcellular fluid exchange. Plasma volume restoration in acute hypo- and hypervolemia is quite effectively accomplished by α- and β-adrenergic nervous and humoral mechanisms which control capillary hydrostatic pressure and capillary exchange surface via influences on vascular smooth muscle tone. The fluid replacement in hypovolemia is reinforced by an adrenergic glucose-osmotic mechanism which adjusts interstitial and intravascular volumes by causing transcellular and transcapillary fluid movements, the latter in tissues with continuous capillary endothelium. Untoward transcapillary fluid shifts during changes of central arterial or venous pressure or during hydrostatic load on the vascular bed are largely prevented by local vascular regulatory mechanisms, especially the myogenic ones. The mode of operation of the myogenic vascular control system is tentatively discussed in the light of some recent studies of myogenic cellular mechanisms.

Effects of the combined ETA and ETB receptor antagonist PD145065 on arteries, arterioles, and veins in the cat hindlimb

Summary: The aim of this study was to describe in quantitative terms the effects of ETA and ETB receptor blockade on vascular tone (resistance) in large-bore arterial resistance vessels (<25 μm), small arterioles (<25 μm), and veins in the cat gastrocnemius muscle in vivo. In the muscle vascular bed, the combined ETA and ETB receptor antagonist PD 145065 (1 mg/kg/min, intra-arterially) abolished the biphasic vascular responses (dilatation followed by constriction) to both ET-1 (0.4 (jig/kg/min, intra-arterially) and to the selective ETB receptor agonist IRL1620 (3.2 μg/kg/min, intra-arterially). In the cat femoral artery and vein in vitro, PD 145065 competitively inhibited the contractile responses to both ET-1 and IRL1620. The contractile response to the latter agonist could be evoked only after long-term incubation of the vessels (37°C for 5 days). These results indicate that PD145065 is a potent antagonist at both ETA and ETB receptors in vivo and in vitro. Therefore, this antagonist may prove useful for elucidating the possible physiologic and/or pathophysiologic roles of the endothelins. For example, it was shown that PD 145065 had no effect on vascular tone in the resting state, indicating no role for the endothelins in the regulation of basal vascular tone in cat skeletal muscle.

NERVOUS CONTROL OF THE MICROCIRCULATION IN SKELETAL MUSCLE

Publisher Summary The vascular bed of skeletal muscle is one of the most important targets for the central nervous sympathetic control of the peripheral circulation. This regulation in skeletal muscle is effected via an alpha-adrenergic, a beta-adrenergic, and a cholinergic link with partly different central representation and different functional organization in the periphery. The alpha-adrenergic constrictor component exerts its main control on large and small precapillary resistance vessels and on capacitance vessels; the beta-adrenergic dilator component exerts a preferential control on small pre- and post-capillary resistance vessels and on precapillary sphincter vessels; and the cholinergic dilator component exerts a relatively selective control of the large-bore precapillary resistance vessels. The chapter focuses on the microvascular beta-adrenergic dilator component. The vasomotor fiber control of peripheral vascular functions primarily subserves general circulatory homeostasis. The adjustment of capillary pressure forms the basis for reflex vasomotor control of plasma volume by determining the fluid distribution between the extravascular and the intravascular spaces.