The role of several α₁‐ and α₂‐adrenoceptor subtypes mediating vasoconstriction in the canine external carotid circulation

Abstract

1 It has recently been shown that both a 1 -and a 2 -adrenoceptors mediate vasoconstriction in the canine external carotid circulation. The present study set out to identify the speci®c subtypes (a 1A , a 1B and a 1D as well as a 2A , a 2B and a 2C ) mediating the above response. 2 Consecutive 1 min intracarotid infusions of phenylephrine (a 1 -adrenoceptor agonist) and BHT933 (a 2 -adrenoceptor agonist) produced dose-dependent decreases in external carotid blood ow, without aecting mean arterial blood pressure or heart rate. 3 The responses to phenylephrine were selectively antagonized by the antagonists, 5-methylurapidil (a 1A ) or BMY7378 (a 1D ), but not by L-765,314 (a 1B ), BRL44408 (a 2A ), imiloxan (a 2B ) or MK912 (a 2C ). In contrast, only BRL44408 or MK912 aected the responses to BHT933. 4 The above results support our contention that mainly the a 1A , a 1D , a 2A and a 2C -adrenoceptor subtypes mediate vasoconstriction in the canine external carotid circulation.

Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

“…Abound et al (1993) showed that the administration of 5-methylurapidil, benoxanthian, and WB 4101 to the incubation chamber decreased the aorta contraction strength in rats in response to noradrenaline. Blockade of the α 1B -adrenergic receptor by addition of L-765.314 did not have any influence on tissue reaction to phenylephrine (Willems et al 2001) which is not in agreement with our results. The role of α 1B -adrenergic receptor in arteries vasoconstriction in dogs seems controversial.…”

“…In vivo studies showed that stimulation of the α 1 -adrenergic receptor by intravenous phenylephrine caused constriction of the arterial vessels in pigs and dogs (Willems et al 2001). The researchers showed a significant increase in the muscle tonus of the arterial vessels, leading to an increased arterial blood pressure of the examined animals.…”

“…According to Willems et al (2001), phenylephrine influences the contractility of the carotid arteries and aorta in dogs, especially by means of α 1A -and α 1D -adrenergic receptors; the α 1B subtype is less significant for aortic contractility. Abound et al (1993) showed that the administration of 5-methylurapidil, benoxanthian, and WB 4101 to the incubation chamber decreased the aorta contraction strength in rats in response to noradrenaline.…”

“…This is one of the mechanisms allowing for blood pressure regulation (Stephenson and Summers 1987;Willems et al 2001). Sympathetic nervous system overactivity is one of the mechanisms playing role in the development of hypertension, which disrupts the function of many organs and leads to remodelling of the arterial wall (Kochová et al 2009).…”

Current and prospective pharmacological targets in relation to antimigraine action

“…Studies on these models showed that the canine carotid vascular responses to the α 2 -adrenoceptor agonist BHT933 were markedly attenuated by the α 2A -adrenoceptor antagonist BRL44408 or the α 2C -adrenoceptor antagonist MK912 (given either alone or in combination) but remained unaffected after administration of the α 2B -adrenoceptor antagonist imiloxan. Figure 3 (right panel) illustrates the effect of α 2 -adrenoceptor subtypes in the canine carotid vascular bed (Willems et al 2001a). Similarly, the carotid vasoconstrictor responses produced by BHT933 in anesthetized pigs were markedly attenuated by MK912, while the other antagonists were ineffective .…”