Postjunctional α2-adrenoceptors in blood vessels: effect of age

doi:10.1016/0014-2999(93)90283-N

European Journal of Pharmacology

Volume 237, Issues 2–3, 24 June 1993, Pages 311-316

https://doi.org/10.1016/0014-2999(93)90283-N Get rights and content

Abstract

To investigate the impact of age on function of vascular postjunctional α₂-adrenoceptors in tail arteries of F-344 rats aged 6 and 20 months, vasoconstrictor responses of isolated ring segments were studied. In both 6 and 20 month old animals, norepinephrine concentration response curves were significantly shifted to the right in the presence of the α₂-adrenoceptor antagonists idazoxan (300 nM) or rauwolscine (50 nM). Furthermore, in both age groups α₂-adrenoceptor agonists UK14304 (300 nM) or BHT920 (25 nM) produced significant enhancements in the vasoconstrictor response to the selective α₁-adrenoceptor agonist, methoxamine. Concentration response curves for norepinephrine and methoxamine were not different with age. These data verify the existence of postjunctional α₂-adrenoceptors and demonstrate that the function of these receptors does not change with age. This supports the proposition that overall vascular adrenergic function in blood vessels is maintained with advancing age.

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Cited by (22)

Characterization of α<inf>2</inf>-adrenoceptors in smooth muscles of the spontaneously hypertensive rat aorta
2003, Vascular Pharmacology
Previous works have shown that the α₂-adrenoceptor agonist UK 14,304 induced the relaxation and hyperpolarization of the rat aorta, mediated by α₂-adrenoceptors present in the smooth muscles, through small-conductance, ATP-sensitive K⁺ channels. We now report that in spontaneously hypertensive rat (SHR) aortic rings, UK 14,304 induced concentration-dependent hyperpolarizing responses, which were inhibited by yohimbine, an α₂-adrenoceptor inhibitor, and by glibenclamide, a specific inhibitor of small-conductance, ATP-sensitive K⁺ channels. The responses were also partially inhibited by iberiotoxin and by apamin. Treatment with N^ω-nitro-l-arginine (l-NNA) did not affect the response to UK 14,304. These results indicate that α₂-adrenoceptors are present in SHR aortic smooth muscle cell membranes, but differ from those of normotensive animals regarding the K⁺ channels involved in their responses. Moreover, the resting membrane potential (RMP) was significantly more negative in SHR than in normotensive rats. This relative hyperpolarized state is probably due to Ca²⁺-dependent K⁺ channels being constitutively open in SHR, since the addition of iberiotoxin caused a significant depolarization of the aortic smooth muscle membranes in this strain.
Different contractile effects of α<inf>1</inf>- and α<inf>2</inf>-adrenergic agonists on horse isolated common digital artery smooth muscle ring preparations In vitro
2002, Pharmacological Research
Despite assays on ring preparations in vitro confirmed that the vasoconstrictor sympathetic control in the horse common digital artery mainly depends on α₁-adrenoceptors stimulation, selective α₂-adrenoceptor agonists were investigated under the same experimental conditions. Both detomidine (DET) and UK 14304 differed from noradrenaline (NA) and phenylephrine (PHE) in provoking contractile effects which were slowly onsetting, concentrations-unrelated and unremovable by repeated washings.
While prazosin (PRA) clearly antagonized the effects of NA and PHE, neither pre- nor post-treatments of the preparations with α₂-antagonists succeeded in antagonizing or removing the effects of the two α₂-agonists tested, which moreover were unaffectable either by lowering the organ bath temperature or by depriving the nutritive medium of Ca²⁺. To explain this unusual behavior of α₂-adrenoceptors stimulation it has been hypothesized that a Ca²⁺ mobilization from the endoplasmic reticulum of the smooth muscle cell occurs which is followed by a hindered reuptake of them.
Postjunctional α<inf>2</inf>-adrenoceptors in the rat tail artery: Effect of sex and castration
1999, European Journal of Pharmacology
To investigate sex-related differences in vasoconstrictor responses to postjunctional α₂-adrenoceptor activation, isolated ring segments of tail arteries from Fischer-344 rats were studied. Addition of the α₂-adrenoceptor agonist, UK-14304 [5-bromo-6-(2-imidazoline-2yl)-aminol-quinoxaline], enhanced vasoconstriction to the selective α₁-adrenoceptor agonist, methoxamine, in arteries from both males and females. The response to UK-14304 was significantly greater in arteries from males as compared to female arteries. Addition of α₂-adrenoceptor antagonist, idazoxan or rauwolscine, shifted norepinephrine concentration response curves to the right. Antagonist effects also tended to be greater in arteries from males as compared to females. After gonadectomy, male–female differences persisted; thus, removal of sex hormones in either males or females did not alter responses to either agonists or antagonists of α₂-adrenoceptors. These findings suggest that sex differences in α₂-adrenoceptor function are not maintained by either male or female gonadal steroid hormones but may be developmentally regulated.
Subtypes of functional α<inf>1</inf>- and α<inf>2</inf>-adrenoceptors
1998, European Journal of Pharmacology
In this review, subtypes of functional α₁- and α₂-adrenoceptors are discussed. These are cell membrane receptors, belonging to the seven transmembrane spanning G-protein-linked family of receptors, which respond to the physiological agonists noradrenaline and adrenaline. α₁-Adrenoceptors can be divided into α_1A-, α_1B- and α_1D-adrenoceptors, all of which mediate contractile responses involving G_q/11 and inositol phosphate turnover. A 4th α₁-adrenoceptor, the α_1L-, has been postulated to mediate contractions in some tissues, but its relationship to cloned receptors remains to be established. α₂-Adrenoceptors can be divided into α_2A-, α_2B- and α_2C-adrenoceptors, all of which mediate contractile responses. Prejunctional inhibitory α₂-adrenoceptors are predominantly of the α_2A-adrenoceptor subtype (the α_2D-adrenoceptor is a species orthologue), although α_2C-adrenoceptors may also occur prejunctionally. Although α₂-adrenoceptors are linked to inhibition of adenylate cyclase, this may not be the primary signal in causing smooth muscle contraction; likewise, prejunctional inhibitory actions probably involve restriction of Ca²⁺ entry or opening of K⁺ channels. Receptor knock-out mice are beginning to refine our knowledge of the functions of α-adrenoceptor subtypes.
Heat acclimation and hypohydration in aged rats: The involvement of adrenergic pathways in thermal-induced vasomotor responses in the portal circulation
1996, Journal of Thermal Biology
- 1.
  1. The beneficial effects of heat acclimation on thermal induced vasomotor responses of hypohydrated aged rats were assessed by measuring the isometric tension of aortic and portal rings of old and young rats under heat acclimation and hypohydration in response to α-adrenergic (α-AR) and β-adrenergic (β-AR) stimulation (phenylephrine 10⁻⁹–10⁻² mM and isoprenaline 10⁻⁹–10⁻⁴ respectively). In parallel, portal blood flow (PBF), which drains the splanchnic vasculature, was measured in conscious rats, before and during heat stress (42°C).
- 2.
  2. In the aorta, heat acclimation augmented phenylephrine (α-AR) induced tension, to a great extent in the older rats. Hypohydration increased α-AR sensitivity in all experimental groups. Acclimation and aging brought about decreased responsiveness in isoprenaline induced relaxation (β-AR) in both the aorta and the portal vein. Hypohydration increased β-AR responsiveness in the portal vein of OR, acclimated and acclimated-hypohydrated rats.
- 3.
  3. Normothermic euhydrated resting PBF was similar for young and old rats. Hypohydration decreased resting PBF. Upon heat stress, thermal induced vasoconstriction in hypohydrated YR and OR occurred earlier than in the euhydrated groups and was more pronounced. The latter responses were attenuated in the old rats.
- 4.
  4. Taken together, these results imply that chronic environmental stressors such as heat acclimation and hypohydration produce selective alterations in AR responsiveness of the vasculature in both young and old rats. Consequently, thermoregulatory vasomotor mediated mechanisms, as exhibited in this study in PBF, may differ in their responsiveness in these two age groups.
Noradrenaline stimulation of high-affinity GTPase activity in membranes from rat aorta and caudal artery
1996, Biochemical Pharmacology
The ability of noradrenaline (NA) to stimulate increases in high-affinity GTPase activity in sarcolemma-enriched rat aorta and caudal artery membranes was examined in the present study. In aortic membranes, NA significantly (P < 0.05; N = 5) increased the V_max from a basal value of 103 ± 29 to 156 ± 38 pmol P_i/min/mg protein, but did not affect the K_m which was 0.32 ± 0.08 μM in the absence and 0.58 ± 0.16 μM in the presence of NA. However, in caudal artery membranes, NA significantly (P < 0.05; N = 6) increased both the V_max and the K_m from basal values of 69 ± 12 pmol P_i/min/mg protein and 0.24 ± 0.05 μM, respectively, to 205 ± 54 pmol P_i/min/mg protein and 1.01 ± 0.25 μM, respectively. Removing the endothelium from both artery preparations did not alter significantly basal GTPase activity or the magnitude of the increase stimulated by NA. Prazosin significantly inhibited NA-stimulated increases in GTPase activity in membranes from endothelium-denuded caudal artery and aorta, and in endothelium-intact caudal artery membranes. However, yohimbine significantly inhibited NA-stimulated increases in GTPase activity only in preparations from endothelium-intact caudal arteries. Therefore, in endothelium-intact caudal artery membranes, NA stimulated increases in GTPase activity that were apparently mediated by both α₁-adrenoceptors and α₂-adrenoceptors, while in endothelium-denuded aortic and caudal artery membranes this increase was mediated solely by α₁-adrenoceptors. Western blotting of these arteries confirmed the presence of both G_{i_α2,3} and $G_{q11α}$ , which are candidates for mediating the α₁-adrenoceptor-stimulated increases in GTPase activity.

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Postjunctional α2-adrenoceptors in blood vessels: effect of age

Abstract

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Alpha-1-adrenergic binding and contraction of rat caudal artery

J. Pharmacol. Exp. Ther.

Effect of age on prejunctional modulation of norepinephrine release

J. Pharmacol. Exp. Ther.

Influence of age on control of norepinephrine release from the rat tail artery

J. Pharmacol. Exp. Ther.

Differential inhibition of vascular smooth muscle responses to α1- and α2-adrenoceptor agonists by diltiazem and verapamil

Circ. Res.

The effect of age on presynaptic alpha2-adrenoceptor autoregulation of norepinephrine release

J. Gerontol.

Cardiovascular responses in ageing: a review

Pharmacol. Rev.

An 3xamination of age-related changes in pre- and post-synaptic α-adrenoceptors in the rat isolated vas deferens

Eur. J. Pharmacol.

Postjunctional α₂-adrenoceptors in blood vessels: effect of age

Differential inhibition of vascular smooth muscle responses to α₁- and α₂-adrenoceptor agonists by diltiazem and verapamil

The effect of age on presynaptic alpha₂-adrenoceptor autoregulation of norepinephrine release