Functional evidence of α<sub>1D</sub>‐adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats

Villalobos‐Molina, Rafael; López-Guerrero, Juan Javier; Ibarra, Maximiliano

doi:10.1038/sj.bjp.0702468

Cited by 63 publications

(36 citation statements)

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“…In addition to our observations, several reports support the idea that ␣ 1D -AR could be involved in the pathogenesis and/or maintenance of hypertension. 19,[27][28][29][30] We observed that 7 ␣ 1D ϩ/ϩ mice died with general edema during 1% saline drinking after subtotal nephrectomy, whereas only 1 ␣ 1D Ϫ/Ϫ mouse died in the same period. This might suggest that ␣ 1D Ϫ/Ϫ mice are less susceptible to acute renal failure caused by subtotal nephrectomy followed by 1% saline drinking.…”

Section: Discussionmentioning

confidence: 99%

“…14 Also, vascular ␣ 1D -AR has been suggested to be related to the pathogenesis/maintenance of hypertension related to aging and SHR. 18,19 Subtotal nephrectomy is a long-accepted experimental procedure 20 that has been used over the years to accentuate salt-induced hypertension equivalent to that accompanying human chronic renal failure. The mechanisms by which salt-loading increases BP are still incompletely understood, but increasing evidence suggests that a neurogenic mechanism is involved in an early interaction between vasopressinergic and adrenergic neurons in the central nervous system (CNS).…”

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confidence: 99%

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Role of the α _1D - Adrenegric Receptor in the Development of Salt-Induced Hypertension

et al. 2002

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Abstract-In an attempt to elucidate whether there is a specific ␣ 1 -adrenergic receptor (␣ 1 -AR) subtype involved in the genesis or maintenance of hypertension, the ␣ 1D -AR subtype was evaluated in a model of salt-induced hypertension. The ␣ 1D -AR-deficient (␣ 1D Ϫ/Ϫ ) and control (␣ 1D ϩ/ϩ ) mice (nϭ8 to 14 in each group) were submitted to subtotal nephrectomy and given 1% saline as drinking water for 35 days. Blood pressure (BP) was monitored by tail-cuff readings and confirmed at the end point by direct intraarterial BP recording. The ␣ 1D Ϫ/Ϫ mice had a significantly (Pϭ0.0004) attenuated increase in BP response in this protocol (baseline 94.6Ϯ2.8 versus end point 107.4Ϯ4.5 mm Hg) compared with that of their wild-type counterparts (␣ 1D ϩ/ϩ ), from a baseline 97.4Ϯ2.9 to an end point 139.4Ϯ4.5 mm Hg. Seven of 15 ␣ 1D ϩ/ϩ mice died with edema, probably owing to renal failure, whereas 14 of 15 ␣ 1D Ϫ/Ϫ mice were maintained for 35 days. Body weight, renal remnant weight, and residual renal function were similar in the 2 groups, whereas the values of plasma catecholamines (epinephrine, norepinephrine, and dopamine) were higher in ␣ 1D ϩ/ϩ than in the ␣ 1D Ϫ/Ϫ mice. These data suggest that ␣ 1D -AR plays an important role in developing a high BP in response to dietary salt-loading, and that agents having selective ␣ 1D -AR antagonism could have significant therapeutic potential in the treatment of hypertension. (Hypertension. 2002;40:101-106.)

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Role of the α _1D - Adrenegric Receptor in the Development of Salt-Induced Hypertension

et al. 2002

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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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“…The prevalence and interaction between adrenoceptors (ARs) responsible for either constriction (␣ 1 -AR and ␣ 2 -AR on VSM) or relaxation (␤-AR on VSM and endothelial ␣ 2 -AR or ␤-AR) can predispose toward altered peripheral resistance and raised blood pressure. [5][6][7][8][9] Moreover, gender-related differences in adrenergic responses have been reported in hypertensive and normotensive subjects. 10 -17 This study was designed to test the hypothesis that hypertension and gender-related differences in blood pressure observed in aging ER␤KO mice could be consequent to modified adrenergic reactivity in peripheral small arteries.…”

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Gender-Specific Alteration of Adrenergic Responses in Small Femoral Arteries From Estrogen Receptor-β Knockout Mice

et al. 2005

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Abstract-Estrogen receptor-␤ knockout mice become hypertensive as they age, and males have a higher blood pressure than females. We hypothesized that the absence of estrogen receptor-␤ may contribute to development of cardiovascular dysfunction by modification of adrenergic responsiveness in the peripheral vasculature. Small femoral arteries (internal diameter Ͻ200 m) were isolated from estrogen receptor-␤ knockout and wild-type mice and mounted on a wire myograph. Concentration-response curves to phenylephrine and norepinephrine were compared and the contribution of adrenoceptor subtypes established using specific agonists and antagonists. The involvement of endothelial factors in the modulation of resting tone was also investigated and immunohistochemical analysis used to confirm the presence or absence of estrogen receptor expression. Compared with wild type, arteries from estrogen receptor-␤ knockout male, but not female, mice demonstrated gender-specific enhancement of the response to phenylephrine (␣ 1 -adrenoceptor agonist), which was accompanied by elevated basal tension attributable to endothelial factors. Contractile responses to the mixed adrenoceptor agonist norepinephrine did not differ significantly between estrogen receptor-␤ knockout and wild type; however, ␤-adrenoceptor inhibition unmasked an enhanced underlying ␣ 1 -adrenoceptor responsiveness in estrogen receptor-␤ knockout males. ␤-adrenoceptor-mediated dilatation was also enhanced in estrogen receptor-␤ knockout versus wild-type males. We suggest that estrogen receptor-␤ modifies the adrenergic control of small artery tone in males but not in females. Key Words: gender Ⅲ endothelium Ⅲ estrogen Ⅲ arteries Ⅲ vasoconstriction Ⅲ adrenergic receptor agonists E ndogenous estrogens are considered to play an important role in cardiovascular homeostasis. Through occupancy of estrogen receptors (ERs) ␣ (ER␣) and ␤ (ER␤), estrogens target genes that contribute to the regulation of vascular tone, the lipid profile, redox status, and vascular structure. However, the relative role of each ER subtype in cardiovascular responses to estrogens remains poorly understood. 1 ER␣ and ER␤ are expressed in the endothelium and in vascular smooth muscle (VSM), but expression of the ER subtypes is gender and vascular bed dependent. 2,3 The explicit role of ER subtypes in the cardiovascular system, particularly in relation to regulation of vascular tone, has been difficult to assess because of the lack of specific ER subtype antagonists or agonists. The development of genetically modified animals in which one or other of the ERs is disrupted provides a useful alternative strategy for investigation. Zhu et al 4 reported that absence of ER␤ leads to age-dependent hypertension in both genders of mice, and that blood pressure in males was higher. However, no mechanisms that could explain gender-related differences in hypertension were proposed, 4 and it is unlikely that the altered contractile function observed in the aorta of the ER␤ knockout (ER␤KO) mice 4 would predisp...

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Functional evidence of α_1D‐adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats

Cited by 63 publications

References 7 publications

Role of the α _1D - Adrenegric Receptor in the Development of Salt-Induced Hypertension

Role of the α _1D - Adrenegric Receptor in the Development of Salt-Induced Hypertension

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

Gender-Specific Alteration of Adrenergic Responses in Small Femoral Arteries From Estrogen Receptor-β Knockout Mice

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Functional evidence of α1D‐adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats

Cited by 63 publications

References 7 publications

Role of the α 1D - Adrenegric Receptor in the Development of Salt-Induced Hypertension

Role of the α 1D - Adrenegric Receptor in the Development of Salt-Induced Hypertension

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

Gender-Specific Alteration of Adrenergic Responses in Small Femoral Arteries From Estrogen Receptor-β Knockout Mice

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Functional evidence of α_1D‐adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats

Role of the α _1D - Adrenegric Receptor in the Development of Salt-Induced Hypertension

Role of the α _1D - Adrenegric Receptor in the Development of Salt-Induced Hypertension