Endothelium-dependent component in the contractile responses of human omental arteries to adrenergic stimulation

doi:10.1016/0014-2999(93)90626-S

European Journal of Pharmacology

Volume 250, Issue 1, 30 November 1993, Pages 103-107

https://doi.org/10.1016/0014-2999(93)90626-S Get rights and content

Abstract

The present study was designed to investigate the influence of endothelium-derived nitric oxide on the contractile responses of isolated human omental arteries to electrical field stimulation and noradrenaline. We measured isometric tension in artery rings obtained from portions of human omentum during the course of abdominal operations (32 patients). Electrical field stimulation induced frequency-dependent contractions which were abolished by tetrodotoxin (10⁻⁶ M) and prazosin (10⁻⁶ M), thus indicating that this effect was due to noradrenaline released from adrenergic nerves acting on α₁-adrenoceptors. The increases in tension induced by electrical field stimulation were of greater magnitude in arteries denuded of endothelium. $N^{G} - Nitro- L -arginine$ (L-NAME, 10⁻⁴ M) potentiated the contractile response to electrical field stimulation in artery rings with endothelium but did not influence the contractile responses of endothelium-denuded arteries. The potentiation induced by L-NAME was completely reversed by L-arginine (10⁻⁴ M), but not by D-arginine (10⁻⁴ M). Contractile responses to noradrenaline were similar in arteries with and without endothelium. L-NAME (10⁻⁴ M) had no significant effect on the contractile responses to noradrenaline. Our results suggest that electrical field stimulation releases endothelium-derived nitric oxide which inhibits the contractile responses of human omental arteries. The constrictor responses to noradrenaline are not modulated by the endothelium.

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Cited by (28)

Effects of endogenous nitric oxide on adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide-containing nerve-mediated vasodilation in pithed rats
2017, European Journal of Pharmacology
Citation Excerpt :
Inhibition of NOS by NOS inhibitors has been reported to augment the vasoconstrictor effects induced by perivascular nerve stimulation in several isolated blood vessels, whereas the enhanced neurogenic responses to NOS inhibitors are reversed by L-arginine, a precursor for the synthesis of NO, and involve the endothelium-derived NO (Toda et al., 1991a, 1991b; Postorino et al., 1998). On the other hand, several studies showed that NOS inhibitors have no effects on vasoconstriction in response to perivascular nerve stimulation in dog pulmonary arteries and human omental arteries without endothelium (Aldasoro et al., 1993; Segarra et al., 1999). In rat mesenteric arteries with endothelium, some reports have described that NOS inhibitors enhanced the vasoconstrictor responses to perivascular nerve stimulation (Yamamoto et al., 1994; Boric et al., 1999), suggesting the involvement of endothelial NO. However, it remains unclear whether perivascular nitrergic nerves modulate adrenergic neurotransmission in vivo.
Vascular adrenergic nerves mainly regulate the tone of blood vessels. Calcitonin gene-related peptide-containing (CGRPergic) vasodilator nerves also participate in the regulation of vascular tone. Furthermore, there are nitric oxide (NO)-containing (nitrergic) nerves, which include NO in blood vessels as vasodilator nerves, but it remains unclear whether nitrergic nerves participate in vascular regulation. The present study investigated the role of nitrergic nerves in vascular responses to spinal cord stimulation (SCS) and vasoactive agents in pithed rats. Wistar rats were anesthetized and pithed, and vasopressor responses to SCS and injections of norepinephrine were observed. To evaluate vasorelaxant responses, the BP was increased by a continuous infusion of methoxamine with hexamethonium to block autonomic outflow. After the elevated BP stabilized, SCS and injections of acetylcholine (ACh), sodium nitroprusside (SNP), and CGRP were intravenously administered. We then evaluated the effects of the NO synthase (NOS) inhibitor, N-ω-nitro-L-arginine methylester hydrochloride (L-NAME), on these vascular responses. Pressor responses to SCS and norepinephrine in pithed rats were enhanced by L-NAME, while the combined infusion of L-NAME and L-arginine had no effect on these responses. L-NAME infusion significantly increased the release of norepinephrine evoked by SCS. In pithed rats with artificially increased BP and L-NAME infusion, depressor response to ACh (except for 0.05 nmol/kg) was suppressed and SNP (only 2 nmol/kg) was enhanced. However, depressor responses to SCS and CGRP were similar to control responses. The present results suggest endogenous NO regulates vascular tone through endothelium function and inhibition of adrenergic neurotransmission, but not through CGRPergic nerves.
Aspirin and COX-2 Inhibitor Nimesulide Potentiate Adrenergic Contractions of Human Gastroepiploic Artery
2007, American Journal of Hypertension
Citation Excerpt :
Electrical field stimulation was provided by a Grass S88 stimulator (Grass Instruments) by two platinum electrodes positioned on each side and parallel to the axis of the vascular ring. To assess the nature of the contractile responses and avoid direct stimulation of smooth muscle, frequency–response relationships were determined in a group of arteries in the presence and absence of 10−6 mol/L tetrodotoxin, following a procedure previously described.19 In summary, the protocol was designed to find the optimal stimulation parameters (15 V, 0.2 msec duration) causing a contractile response that was completely eliminated by 10−6 mol/L tetrodotoxin.
The aim of the present study was to evaluate the intervention of COX-1- and COX-2-derived prostaglandins in the responses of human gastroepiploic artery to sympathetic stimulation and norepinephrine.
Rings of human gastroepiploic artery were obtained from 45 patients (26 men and 19 women) undergoing gastrectomy. The rings were suspended in organ baths for isometric recording of tension. We studied the responses to electrical field stimulation, norepinephrine, and acetylcholine, in the absence and presence of COX-1 or COX-2 inhibition.
The COX-1 and COX-2 inhibitor aspirin at high concentrations (10⁻⁶ to 10⁻⁵ mol/L) and the COX-2 inhibitor nimesulide (10⁻⁶ mol/L) potentiated the contractile responses of the arterial rings to sympathetic neurogenic stimulation and norepinephrine. In contrast, lower concentrations of aspirin (10⁻⁸ to 10⁻⁷ mol/L) or the COX-1 inhibitor SC-560 (3 ×10⁻⁸ mol/L) did not affect these responses. The vascular relaxation induced by acetylcholine was not affected by COX-1 and COX-2 inhibition.
The results provide functional evidence that vasodilator prostaglandins are active components of the response of human gastroepiploic artery to neurogenic stimulation and norepinephrine. Aspirin at high concentrations and the COX-2 selective inhibitor nimesulide potentiated the contractile response of gastroepiploic artery to adrenergic stimulation by inhibiting COX-2-derived PGI₂. Aspirin at low concentrations and the COX-1 selective inhibitor SC-560 did not modify the contractile responses, possibly due to minor importance of vasoconstrictor prostaglandins (TXA₂) as active components of the response of gastroepiploic artery to adrenergic stimulation.
Endothelium-dependent noradrenergic hyperresponsiveness induced by thapsigargin in human saphenous veins: Role of thromboxane and calcium
2004, European Journal of Pharmacology
To further investigate the mechanisms which regulate sympathetic vascular tone, we studied the effects of the sarcoplasmic reticulum Ca²⁺-ATPase inhibitor, thapsigargin, on the vasoconstriction induced by transmural nerve stimulation and noradrenaline in superfused human saphenous vein rings. The contractions induced by both transmural nerve stimulation and noradrenaline were potentiated by thapsigargin in endothelium-intact, but not in endothelium-denuded vessels. This potentiation was unaffected by the non-selective endothelin ET_A/B receptor antagonist, Ro 47-0203 (4-tert-Butyyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2′-bipyrimidin-4yl]benzene sulfonamide), or by the nitric oxide (NO) synthase inhibitor, l-NNA (N^ω-nitro-l-arginine), but was inhibited by the thromboxane A₂ receptor antagonist, Bay u3405 (3(R)-[[(4-flurophenyl) sulphonyl]amino-1,2,3,4-tetrahydro-9H-carbazole-9-propanoic acid]) or by the thromboxane A₂ synthase inhibitor, UK 38485 (3-(1H-imidazol-1-yl-methyl)-2-methyl-1H-indole-1-propanoic acid). Moreover, the thapsigargin-induced noradrenergic hyperresponsiveness, as well as that produced by subthreshold concentrations of the thromboxane A₂ mimetic, U 46619, were blocked by the Ca²⁺ channel antagonist, verapamil. In conclusion, our results indicate that thapsigargin enhances the contractions produced by sympathetic nerve stimulation in human saphenous vein rings through the endothelial release of thromboxane A₂ that potentiates the vasoconstriction induced by the noradrenergic mediator with a verapamil-sensitive mechanism.
Lack of prejunctional modulation of noradrenaline release by endogenous nitric oxide in guinea pig pulmonary artery
2002, Neurochemistry International
The regulation of noradrenaline (NA) release by endogenous endothelium-derived compounds was investigated in the isolated guinea pig pulmonary artery preloaded with [ $^{3} H$ ]NA. The radioactivity uptake, the basal and electrical field stimulation (10 Hz, 2 ms, 360 shocks) evoked release of [ $^{3} H$ ]NA was similar in arteries with intact endothelium and after removal of the endothelium. The wide selectivity nitric oxide (NO) synthase inhibitor N-ω-nitro-l-arginine (100 μM) did not affect significantly the basal and stimulation-evoked release of [ $^{3} H$ ]NA in control and endothelium-denuded preparations. These results indicate that neither endogenous NO nor other compounds derived from the endothelium have substantial influence on the NA outflow from sympathetic nerves innervating the pulmonary artery.
Endothelin-1-induced potentiation of adrenergic responses in the rabbit pulmonary artery: Role of thromboxane A<inf>2</inf>
2001, European Journal of Pharmacology
To examine whether low concentrations of endothelin-1 potentiate the vasocontrictor response to adrenergic stimulation, we recorded the isometric response of rings of rabbit pulmonary artery to electrical stimulation and noradrenaline. Endothelin-1 (10⁻¹⁰ M) potentiated the contractions induced by electrical stimulation and noradrenaline. The endothelin ET_B receptor antagonist (2,6-dimethylpiperidinecarbonyl-γ-methyl-Leu-N_in-[Methoxycarbonyl]-d-Trp-d-Nle) (BQ-788, 10⁻⁶ M), but not the endothelin ET_A receptor antagonist cyclo(d-Asp-Pro-d-Val-Leu-d-TRP) (BQ-123, 10⁻⁶ M), inhibited the potentiating effects of endothelin-1. Pretreatment with the cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor furegrelate and the thromboxane receptor antagonist [1S-[1α,2α(Z),3α,4α]]-7-[3-[[[[(1-oxoheptyl)amino]acetyl]amino] methyl]-7-oxabicyclo-[2.2.1]hept-2-yl]-5-heptenoic acid (SQ-30741) (all at 10⁻⁵ M) prevented the potentiation induced by endothelin-1 on adrenergic stimulation. The Ca²⁺ channel antagonist nifedipine (10⁻⁶ M) did not affect the potentiation induced by endothelin-1. The results indicate that endothelin-1 potentiates the responses to electrical stimulation and noradrenaline by activating endothelin ET_B receptors. This potentiation depends on the production of cyclooxygenase-generated factors, probably thromboxane A₂.
Nitric oxide inhibits norepinephrine stimulated contraction of human internal thoracic artery and rat aorta
2001, Pharmacological Research
The effect of nitric oxide (NO) on norepinephrine-induced vascular contraction was evaluated using segments of rat aorta and human internal thoracic artery (ITA) and the NO donor, SNAP. NO levels were measured directly using an amperometric probe. Concentrations of NO greater than 2 nM were required to reduce vascular contraction induced by 100 nM norepinephrine (NE). Exposure of the aortic rings to SNAP prior to, or after NE addition, resulted in a similar attenuation of NE-induced contraction. In contrast, increased relaxation of ITA segments in response to SNAP was observed relative to that of rat aorta and significant development of contractile tone following NE addition was not observed. Evaluation of cytoskeletal actin demonstrated marked loss of F-actin content in smooth muscle cells following NO exposure, suggesting that NO may have direct and indirect effects on contractile tone. These data taken together suggest that vascular responsiveness to contractile agents may be significantly attenuated by prior or subsequent exposure to NO, and mechanisms in addition to vascular relaxation are likely to contribute to this effect.

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Endothelium-dependent component in the contractile responses of human omental arteries to adrenergic stimulation

Abstract

Life Sci.

Lancet

NG-Nitro L-arginine methyl ester and other alkyl esters of arginine are muscarinic receptor antagonists

Circ. Res.

Increased endothelial cell turnover in areas of in vivo Evans blue uptake in the pig aorta

Atherosclerosis

Aminergic histofluorescence and contractile responses to transmural electrical field stimulation and norepinephrine of human middle cerebral arteries obtained promptly after death

Circ. Res.

Log-normal distribution of equieffective doses of norepinephrine and acetylcholine in several tissues

J. Pharmacol. Exp. Ther.

Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacological and chemical properties that are identical to those of nitric oxide radical

Circ. Res.

Endogenous nitric oxide modulates adrenergic neural vasoconstriction in guinea-pig pulmonary artery

Br. J. Pharmacol.

Endothelium-independent contractions of human cerebral arteries in response to vasopressin

Stroke

Role of endothelium and calcium channels in endothelin-induced contraction of human cerebral arteries

Br. J. Pharmacol.

The discovery of nitric oxide as the endogenous nitrovasodilator

Hypertension

N^G-Nitro L-arginine methyl ester and other alkyl esters of arginine are muscarinic receptor antagonists