Influences of the endothelium and hypoxia on α<sub>1</sub>‐ and α<sub>2</sub>‐adrenoceptor‐mediated responses in the rabbit isolated pulmonary artery

MacLean, Margaret R.; McCulloch, Kirsty; McGrath, J.C.

doi:10.1111/j.1476-5381.1993.tb13456.x

Cited by 39 publications

(30 citation statements)

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“…The underlying mechanism for this phenomenon has still to be determined. We have previously shown that inhibition of nitric oxide synthase also potentiates responses to noradrenaline and the M2-adrenoceptor agonist UK 14304, in both rabbit isolated pulmonary arteries and the rat isolated perfused lung (Shaw et al, 1992;MacLean et al, 1993). The combined effect of the increased sensitivity to nerve stimulation, shown in the present study, and to circulating catecholamines would be likely to aggravate further pulmonary hypertension.…”

Section: Discussionsupporting

confidence: 55%

“…We have shown that transient inhibition of nitric oxide is responsible for the transient vasoconstrictor response to acute hypoxia in rabbit pulmonary arteries (MacLean & McGrath, 1991). Inhibition of nitric oxide synthase with N0-nitro-L-arginine methylester (L-NAME) potentiates post-junctional response to noradrenaline in rabbit pulmonary arteries and the rat perfused lung and in the former, this effect appears to involve X2-adrenoceptor stimulation (Shaw et al, 1992;MacLean et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

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Influences of the endothelium and hypoxia on neurogenic transmission in the isolated pulmonary artery of the rabbit

MacLean

McCulloch

Macmillan

et al. 1993

British J Pharmacology

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1The effects of nitric oxide (10-6 M), NW-nitro-L-arginine methylester (L-NAME, 10-M, an inhibitor of nitric oxide synthase), endothelium removal, hypoxia and selective ax-adrenoceptor antagonists on responses to nerve electrical field-stimulation (EFS) were studied in the rabbit isolated pulmonary artery.2 EFS induced frequency-dependent contractions which were abolished by prazosin (xi-adrenoceptor antagonist) and unaffected by rauwolscine (M2-adrenoceptor antagonist). EFS-induced responses were potentiated by L-NAME and inhibited by nitric oxide. The effect of L-NAME was reversed by the presence of L-arginine (2 x 10-4 M), which had no effect on its own. In the presence of L-NAME, the EFS-induced responses were reduced by rauwolscine and the residual responses were abolished by prazosin. 3 Removal of the vascular endothelium increased the maximum contractile response to EFS but did not inhibit the ability of L-NAME to potentiate contractile responses to EFS. 4 Hypoxia inhibited the contractile response to EFS. This effect of hypoxia was also seen in the presence of L-NAME and in endothelium rubbed preparations. 5 In conclusion, the endothelium modulates EFS-induced contractions in the rabbit pulmonary artery. The contraction induced by EFS was inhibited by nitric oxide, but potentiated by the nitric oxidesynthase inhibitor, L-NAME. The effect of L-NAME was not mediated solely through the endothelium and revealed involvement of a2-adrenoceptors in EFS-induced contraction. Hypoxia inhibited neurogenic responses in rabbit isolated pulmonary arteries.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Influences of the endothelium and hypoxia on neurogenic transmission in the isolated pulmonary artery of the rabbit

MacLean

McCulloch

Macmillan

et al. 1993

British J Pharmacology

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“…We reported that norepinephrine infusion induces a potent NO-dependent pulmonary vasodilation in fetal lambs (17). As ␣ 2 -adrenoceptor antagonists were found to inhibit norepinephrine-mediated relaxation of pulmonary (16,18) or systemic arteries (15), or enhance norepinephrine-mediated pulmonary vasoconstrictive response (8,9), norepinephrine-mediated pulmonary vasodilation may result from activation of endothelial ␣ 2 -adrenoceptors.…”

mentioning

confidence: 98%

“…The vasodilator action of several substances, such as acetylcholine, bradykinin, or ADP, and shear stress are dependent, at least in part, on NO release (6). More recently, in vitro studies reported that NO release and pulmonary vasorelaxation can also be mediated by endothelial ␣ 2 -adrenoceptor activation (7)(8)(9). However, little is known about the role of ␣ 2 -adrenoceptors on the basal pulmonary vascular tone during fetal life and on the adaptation of the pulmonary circulation at birth.…”

mentioning

confidence: 99%

Role of the Alpha2-Adrenoceptors on the Pulmonary Circulation in the Ovine Fetus

et al. 2003

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Recent in vitro studies reported that nitric oxide release and pulmonary vasorelaxation can be mediated by endothelial ␣ 2 -adrenoceptor activation. As norepinephrine (␣ 1 -,␣ 2 -, and ␤ 1 -adrenoceptor agonist) was found to induce pulmonary vasodilation in the ovine fetus, we hypothesized that ␣ 2 -adrenoceptors may modulate basal pulmonary vascular tone and mediate the vascular effect of norepinephrine during fetal life. To determine the role of ␣ 2 -adrenoceptors and the mechanisms of norepinephrine-mediated vasodilation in the fetal pulmonary circulation, we tested, in chronically prepared late-gestation fetal lambs, the hemodynamic response to 1) yohimbine (␣ 2 antagonist); 2) UK 14,304 (␣ 2 agonist) with and without L-nitro-arginine (nitric oxide synthase inhibitor); and 3) norepinephrine infusion with and without yohimbine. We found that yohimbine increased mean pulmonary artery pressure by 15% (p Ͻ 0.05), decreased pulmonary flow by 22% (p Ͻ 0.01), and increased pulmonary vascular resistance by 51% (p Ͻ 0.01). UK 14,304 increased pulmonary flow by 145% (p Ͻ 0.01) and decreased pulmonary vascular resistance by 58% (p Ͻ 0.01). L-Nitro-arginine abolished the UK 14,304-mediated pulmonary vasodilation. Norepinephrine (0.5 g·kg Ϫ1 ·min Ϫ1 ) increased both pulmonary flow by 61% (p Ͻ 0.01) and pulmonary arterial pressure by 13% (p Ͻ 0.01) and decreased pulmonary vascular resistance by 33% (p Ͻ 0.01). Yohimbine abolished the norepinephrine-induced pulmonary vasodilation. This study suggests that 1) a basal ␣ 2 -adrenoceptor activation-induced pulmonary vasodilation exists during fetal life; 2) the pulmonary vascular effects of ␣ 2 -adrenoceptor activation are related at least in part to nitric oxide production; and 3) the norepinephrine-mediated pulmonary vasodilation involves ␣ 2 -adrenoceptor activation. As a surge of norepinephrine exists at birth, we speculate that norepinephrine and endothelial ␣ 2 -adrenoceptor activation may play a significant role in pulmonary vasodilation at birth. High resistance and low blood flow characterize the fetal pulmonary circulation. PVR decreases dramatically during the normal transition from the fetal to neonatal circulation at birth. Three main factors contribute to the increase of Q p during this transition: ventilation of the lung (1), increased O 2 (2), and hemodynamic forces, such as increased shear stress (3). Vasoactive mediators released from the endothelium, such as NO, play a major role in the regulation of acute changes in vascular tone in the perinatal lung, and in many cases, modulate the pulmonary vascular response to these birth-related stimuli (4). Inhibition of NO synthesis can attenuate the postnatal adaptation of the pulmonary circulation (5). The vasodilator action of several substances, such as acetylcholine, bradykinin, or ADP, and shear stress are dependent, at least in part, on NO release (6). More recently, in vitro studies reported that NO release and pulmonary vasorelaxation can also be mediated by endothelial ␣ 2 -adrenoceptor activation (7-9). Ho...

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“…This could have functional signi®cance, as sympathetic stimulation causes changes in pulmonary vascular resistance that are mediated via noradrenaline and a-and b-adrenoceptors (Hyman et al, 1990). We have previously shown that relaxation of PGF 2a constricted rat pulmonary arteries by b-adrenoceptor agonists is largely endothelium dependent and mediated via nitric oxide (NO) (Priest et al, 1997), and there is evidence that noradrenaline-induced vasoconstriction of pulmonary arteries may be depressed due to stimulation of NO synthesis via both a-and b-adrenoceptors (MacLean et al, 1993;Tulloh et al, 1994;Priest et al, 1997). Constriction of porcine pulmonary arteries with the a 1 -adrenoceptor agonist phenylephrine (PE) has also been associated with an endothelium-dependent rise in cyclic GMP (Pepke-Zaba et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Potentiation of cyclic AMP‐mediated vasorelaxation by phenylephrine in pulmonary arteries of the rat

Priest

Hucks

Ward

1999

British J Pharmacology

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1 a 1 -adrenoceptor agonists may potentiate relaxation to b-adrenoceptor agonists, although the mechanisms are unclear. We compared relaxations induced by b-adrenoceptor agonists and cyclic AMP-dependent vasodilators in rat pulmonary arteries constricted with prostaglandin F 2a (PGF 2a ) or the a 1 -adrenoceptor agonist phenylephrine (PE). In addition, we examined whether di erences were related to cyclic AMP-or nitric oxide (NO) and cyclic GMP-dependent pathways. 2 Isoprenaline-induced relaxation was substantially potentiated in arteries constricted with PE compared with PGF 2a . Methoxamine was similar to PE, whereas there was no di erence between PGF 2a and 30 mM KCl. The potentiation was primarily due to a marked increase in the NOindependent component of relaxation, from 9.1+1.7% for PGF 2a to 55.1+4.4% for PE. NOdependent relaxation was also enhanced, but to a lesser extent (*50%). Relaxation to salbutamol was almost entirely NO-dependent in both groups, and was potentiated *50% by PE. 3 Relaxation to forskolin (activator of adenylate cyclase) was also enhanced in PE constricted arteries. Part of this relaxation was NO-dependent, but the major e ect of PE was to increase the NO-independent component. Propranolol diminished but did not abolish the potentiation. There was no di erence in response to CPT cyclic AMP (membrane permeant analogue) between PE and PGF 2a , suggesting that mechanisms distal to the production of cyclic AMP were unchanged. 4 Relaxation to sodium nitroprusside (SNP) was the same for PE and PGF 2a , although relaxation to acetylcholine (ACh) was slightly depressed. This implies that potentiation by PE does not involve the cyclic GMP pathway directly. 5 Mesenteric arteries constricted with PE did not show potentiation of isoprenaline-induced relaxation compared to those constricted with PGF 2a , suggesting that this e ect may be speci®c to the pulmonary circulation. 6 These results clearly show that PE potentiates both the NO-independent and -dependent components of cyclic AMP-mediated relaxation in pulmonary arteries of the rat, although the e ect on the former is more profound. We suggest that potentiation of both components is largely due to direct activation of adenylate cyclase via a 1 -adrenoceptors, within the smooth muscle and endothelial cells respectively.

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Influences of the endothelium and hypoxia on α₁‐ and α₂‐adrenoceptor‐mediated responses in the rabbit isolated pulmonary artery

Cited by 39 publications

References 27 publications

Influences of the endothelium and hypoxia on neurogenic transmission in the isolated pulmonary artery of the rabbit

Influences of the endothelium and hypoxia on neurogenic transmission in the isolated pulmonary artery of the rabbit

Role of the Alpha2-Adrenoceptors on the Pulmonary Circulation in the Ovine Fetus

Potentiation of cyclic AMP‐mediated vasorelaxation by phenylephrine in pulmonary arteries of the rat

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Influences of the endothelium and hypoxia on α1‐ and α2‐adrenoceptor‐mediated responses in the rabbit isolated pulmonary artery

Cited by 39 publications

References 27 publications

Influences of the endothelium and hypoxia on neurogenic transmission in the isolated pulmonary artery of the rabbit

Influences of the endothelium and hypoxia on neurogenic transmission in the isolated pulmonary artery of the rabbit

Role of the Alpha2-Adrenoceptors on the Pulmonary Circulation in the Ovine Fetus

Potentiation of cyclic AMP‐mediated vasorelaxation by phenylephrine in pulmonary arteries of the rat

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Influences of the endothelium and hypoxia on α₁‐ and α₂‐adrenoceptor‐mediated responses in the rabbit isolated pulmonary artery