Pathological role of a constitutively active population of α_1D‐adrenoceptors in arteries of spontaneously hypertensive rats

Abstract

1 The role of a constitutively active population of a 1D -adrenoceptors was analysed in arteries obtained from spontaneously hypertensive rats (SHR) and controls (WKY) divided into three groups: young prehypertensive, adult hypertensive, and adult animals chronically treated with captopril (50 mg kg 71 per day orally) in order to prevent the hypertensive state. 2 In adult SHR, a signi®cant increase in BMY 7378 potency (not in prazosin potency) was observed in aorta, mesenteric artery, and the ®rst and second branches of the small mesenteric arteries with respect to WKY rats. This di erence was not observed in iliac and tail arteries, which suggests an increased functional role of a 1D -adrenoceptors only in some vessels of SHR. 3 The increase in the resting tone (IRT) observed in absence of agonist, inhibited by BMY 7378, that represents the constitutively active population of a 1D -adrenoceptors, was also signi®cantly greater in aorta and mesenteric artery from adult SHR. 4 In young and captopril treated adult animals, no di erences between strains with respect to BMY 7378 potency, or IRT were observed. 5 The increase in the functional role of a 1D -adrenoceptors and their constitutive activity observed in hypertension is prevented by captopril treatment. The pathological consequence of this change is the slower rate of recovery of the basal tone after removal of an adrenergic stimulus, observed in vessels from hypertensive animals that had shown an increase in the functionality of constitutively active a 1D -adrenoceptors. This change was not observed in prehypertensive or captopril treated animals. IRT, increase in the resting tone; NA, noradrenaline; SHR, spontaneously hypertensive rats; SMA-1 and SMA-2, ®rst and second small mesenteric arterial branches; WKY, Wistar Kyoto rats

The Impact of α1-Adrenoceptors Up-Regulation Accompanied by the Impairment of β-Adrenergic Vasodilatation in Hypertension

“…As shown in Table 3 and Fig. 6, a significant increase in the potency (pIC 50 ) of the selective ␣ 1D antagonist BMY 7378 was seen in aortas from adult SHRs versus WKY animals confirming the major functional role of the ␣ 1D -ARs previously reported in aorta from adult hypertensive rats but not in young animals (previous results, Gisbert et al, 2002). However, no such change was found with the selective ␣ 1A antagonist 5-methylurapidil (Table 3; Fig.…”

“…An increased functional role of ␣ 1D -ARs has been proposed as one of the changes involved in the hypertensive increase of vascular resistance (VillalobosMolina et al, 1999;Gisbert et al, 2002;Tanoue et al, 2002a,b;Ziani et al, 2002;D'Ocon, 2003;Lyssand et al, 2008), but the mechanism responsible for this increase has not been elucidated previously.…”

Changes in Adrenoceptors and G-Protein-Coupled Receptor Kinase 2 in <smlcap>L</smlcap>-NAME-Induced Hypertension Compared to Spontaneous Hypertension in Rats

“…In the MRA of LNHR, no significant changes in either the CRCs of phenylephrine or the expression of α 1 -ARs were found, as reported in SHR [34] and as the present results show. Thus the α 1 -adrenergic response in MRA is not influenced by hypertension or chronic L -NAME treatment.…”

“…As previously reported [12], the greater potency of phenylephrine observed in the aortas of SHR can determine the pathological increase in tone linked to the genesis of the hypertensive state. This increased sensitivity correlates not only with a significant increase in the expression of the three α 1 -AR subtypes in the aorta [12] but also with an increase in α 1D -AR functionality, which is the main subtype in this vessel [15,34,35,36,37], with a major affinity for agonists [15,38]. …”

Adenosinergic System in the Mesenteric Vessels

“…Other studies have found differences in blood vessels when comparing SHR and WKY (Cox, 1979;Gisbert et al, 2002;Leal et al, 2008;Lee, 1987); Rocha-Pereira et al, 2009). Findings from the study by Gisbert and co-workers (2002), showed that the population of constitutively active α 1D -adrenoceptors is significantly increased in aorta and mesenteric www.intechopen.com artery from adult SHR when compared to WKY -these results verify that the vessels in question, from hypertensive animals, have an increased population of constitutively active receptors as well as an increased functionality of the α 1D -subtype, with respect to normotensive animals.…”