α1-Adrenoceptors mediating contraction in arteries of normotensive and spontaneously hypertensive rats are of the α1D or α1A subtypes

Villalobos‐Molina, Rafael; Ibarra, Maximiliano

doi:10.1016/0014-2999(95)00781-4

Cited by 88 publications

(59 citation statements)

References 12 publications

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“…Enhanced activity of the α 1D -AR has been suggested to be involved in the pathogenesis and/or maintenance of hypertension (45)(46)(47) and age-related changes in vascular responsiveness (48) and also other physiological effects, such as vascular smooth muscle cell growth and hypertrophy (49,50). The α 1D -AR knockout mice would be of value in studying mechanisms involved in the control of vascular physiology and its dysregulation.…”

Section: Discussionmentioning

confidence: 99%

The α1D-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction

Tanoue¹,

Nasa²,

Koshimizu³

et al. 2002

J. Clin. Invest.

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To investigate the physiological role of the α1D-adrenergic receptor (α1D-AR) subtype, we created mice lacking the α1D-AR (α1D–/–) by gene targeting and characterized their cardiovascular function. In α1D–/– mice, the RT-PCR did not detect any transcript of the α1D-AR in any tissue examined, and there was no apparent upregulation of other α1-AR subtypes. Radioligand binding studies showed that α1-AR binding capacity in the aorta was lost, while that in the heart was unaltered in α1D–/– mice. Non-anesthetized α1D–/– mice maintained significantly lower basal systolic and mean arterial blood pressure conditions, relative to wild-type mice, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. Besides hypotension, the pressor responses to phenylephrine and norepinephrine were decreased by 30–40% in α1D–/– mice. Furthermore, the contractile response of the aorta and the pressor response of isolated perfused mesenteric arterial beds to α1-AR stimulation were markedly reduced in α1D–/– mice. We conclude that the α1D-AR participates directly in sympathetic regulation of systemic blood pressure by vasoconstriction

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Section: Discussionmentioning

confidence: 99%

The α1D-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction

Tanoue¹,

Nasa²,

Koshimizu³

et al. 2002

J. Clin. Invest.

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“…Activation of a 1A -adrenoceptors causes constriction of the renal vascular resistance bed (afferent and efferent arterioles) in the Wistar, Stroke-Prone Spontaneously Hypertensive Rats (SHRSP), Two kidney One Clip (2K1C) and Deoxycorticosterone acetate-Salt (DOCA-Salt) hypertensive rats, while the a 1B adrenoceptor subtype seems to play a lesser role (Sattar & Johns, 1994a, b). Other studies reported that the renal adrenergic vasoconstrictor responses are mediated by a 1A - (Elhawary et al, 1992;Blue et al, 1995;Villalobos-Molina & Ibarra, 1997) and/or via a 1D -adrenoceptor subtypes (Villalobos-Molina & Ibarra, 1996;1997), although Piascik et al (1995) suggested that the a 1D -adrenoceptor subtype did not appear to play a role in mediating contraction of this vessel.…”

Section: Introductionmentioning

confidence: 96%

The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats

Armenia

Munavvar

Abdullah

et al. 2004

British J Pharmacology

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1 Diabetes and hypertension are both associated with an increased risk of renal disease and are associated with neuropathies, which can cause defective autonomic control of major organs including the kidney. This study aimed to examine the a 1 -adrenoceptor subtype(s) involved in mediating adrenergically induced renal vasoconstriction in a rat model of diabetes and hypertension. 2 Male spontaneously hypertensive rats (SHR), 220-280 g, were anaesthetized with sodium pentobarbitone 7-day poststreptozotocin (55 mg kg À1 i.p.) treatment. The reductions in renal blood flow (RBF) induced by increasing frequencies of electrical renal nerve stimulation (RNS), close intrarenal bolus doses of noradrenaline (NA), phenylephrine (PE) or methoxamine were determined before and after administration of nitrendipine (Nit), 5-methylurapidil (5-MeU), chloroethylclonidine (CEC) and BMY 7378. 3 In the nondiabetic SHR group, mean arterial pressure (MAP) was 14676 mmHg, RBF was 28.071.4 ml min À1 kg À1 and blood glucose was 112.374.7 mg dl À1, and in the diabetic SHR Group, MAP was 14473 mmHg, RBF 26.971.3 ml À1 min kg À1 and blood glucose 316.2710.5 mg dl À1. Nit, 5-MeU and BMY 7378 blunted all the adrenergically induced renal vasoconstrictor responses in SHR and diabetic SHR by 25-35% (all Po0.05), but in diabetic rats the responses induced by RNS and NA treated with 5-MeU were not changed. By contrast, during the administration of CEC, vasoconstrictor responses to all agonists were enhanced by 20-25% (all Po0.05) in both the SHR and diabetic SHR. 4 These findings suggest that a 1A and a 1D -adrenoceptor subtypes contribute in mediating the adrenergically induced constriction of the renal vasculature in both the SHR and diabetic SHR. There was also an indication of a greater contribution of presynaptic adrenoceptors, that is, a 1B -, and/or a 2 -subtypes.

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“…The ␣ 1 -ARs present in vessels (␣ 1A , ␣ 1B , ␣ 1D ) not only play an essential role in the modulation of the vascular tone but also in the regulation of blood pressure through their vasoconstrictor activity (Piascik et al, 1995;Noguera et al, 1996;Villalobos-Molina and Ibarra, 1996;Hrometz et al, 1999;Gisbert et al, 2000Gisbert et al, , 2003b. 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.…”

mentioning

confidence: 99%

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

Oliver

Martí²,

Montó³

et al. 2008

J Pharmacol Exp Ther

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In human and animal hypertension models, increased activity of G-protein-coupled receptor kinase (GRK) 2 determines a generalized decrease of ␤-adrenergic vasodilatation. We analyzed the possibility of differential changes in the expression and functionality of ␣ 1A , ␣ 1B , ␣ 1D , ␤ 1 , ␤ 2 , and ␤ 3 -ARs also being involved in the process. We combined the quantification of mRNA levels with immunoblotting and functional studies in aortas of young and adult spontaneously hypertensive rats (SHRs) and their controls (Wistar Kyoto). We found the expression and function of ␤ 1 -adrenoceptors in young prehypertensive SHRs to be higher, whereas a generalized increase in the expression of the six adrenoceptors and GRK2 was observed in aortas of adult hypertensive SHRs. ␣ 1D -and ␤ 3 -Adrenoceptors, the subtypes that are more resistant to GRK2-mediated internalization and mostly expressed in rat aorta, exhibited an increased functional role in hypertensive animals, showing two hemodynamic consequences: 1) an increased sensitivity to the vasoconstrictor stimulus accompanied by a decreased sensitivity to the vasodilator stimulus (␣ 1D -ARs are the most sensitive to agonists, and ␤ 3 -ARs are the least sensitive to agonists); and 2) a slower recovery of the basal tone after adrenergic stimulus removal because of the kinetic characteristic of the ␣ 1D subtype. These functional changes might be involved in the greater sympathetic vasoconstrictor tone observed in hypertension.Although there is growing evidence that essential hypertension is related to the overactivity of the sympathetic nervous system, the exact causes are still poorly understood. The adrenergic-dependent increase in vascular resistance could reflect an imbalance between vasoconstrictor and vasodilator mechanisms related to changes in both the expression and function of ␣ 1 -adrenoceptors (ARs), which mediate vasoconstriction, ␤-ARs, which mediate vasodilatation, and/or changes in G-protein-coupled receptor kinases (GRKs), the key regulators of the ␤-ARs (Feldman and Gros, 2006;Penela et al., 2006).

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α1-Adrenoceptors mediating contraction in arteries of normotensive and spontaneously hypertensive rats are of the α1D or α1A subtypes

Cited by 88 publications

References 12 publications

The α1D-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction

The α1D-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction

The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats

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

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α1-Adrenoceptors mediating contraction in arteries of normotensive and spontaneously hypertensive rats are of the α1D or α1A subtypes

Cited by 88 publications

References 12 publications

The α1D-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction

The α1D-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction

The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats

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

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