Ligustrazine‐induced endothelium‐dependent relaxation in pulmonary arteries via an NO‐mediated and exogenous L‐arginine‐dependent mechanism

Peng, Weijun; Hucks, D.; Priest, Rachel M.; Kan, Yanqing; Ward, Jeremy P. T.

doi:10.1111/j.1476-5381.1996.tb15778.x

Cited by 45 publications

(33 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was noticeable that in small arteries the maximum relaxation to isoprenaline was signi®cantly less in the presence of phentolamine, and, although not commented upon in the paper, relaxation to isoprenaline has been shown to be greater in mesenteric arteries constricted with noradrenaline than with K + (Graves & Poston, 1993).We have also found that endothelium-dependent relaxation is greater following constriction with phenylephrine as compared to PGF 2a or KPSS (Peng et al, 1996). These results imply that a-adrenoceptor stimulation might potentiate NO-mediated relaxation, although the mechanism remains to be elucidated.…”

Section: Discussionsupporting

confidence: 53%

Noradrenaline, β‐adrenoceptor mediated vasorelaxation and nitric oxide in large and small pulmonary arteries of the rat

Priest¹,

Hucks²,

Ward³

1997

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

1 Noradrenaline induces a meagre vasoconstriction in small muscular pulmonary arteries compared to large conduit pulmonary arteries. We have examined whether this may be partially related to di erences in the b-adrenoceptor-mediated vasorelaxation component and, in particular, b-adrenoceptor-mediated NO release. 2 Noradrenaline induced a bell-shaped concentration-response in large (1202+27 mm) and small (334+12 mm) pulmonary arteries of the rat. In large arteries tension increased to 95.6+1.8% of 75 mM KCl (KPSS; n=8) at 2 mM, above which tension declined. The response in small arteries was meagre (12+1.5% KPSS, n=9), peaking at 0.2 mM. N G -monomethyl-L-arginine (L-NMMA; 100 mM) abolished the decline in tension induced by higher concentrations of noradrenaline in large arteries, and increased maximum tension (117+3.5% KPSS, n=5, P50.05). In small arteries peak tension doubled (22.0+3.4% KPSS, n=6, P50.01), but still declined above 0.2 mM. 3 Propranolol (1 mM) abolished the decline in tension at higher concentrations of noradrenaline in both groups, but increased tension substantially more in small (37.4+3.7% KPSS, n=5, P50.001) than in large arteries (112.2+3.7% KPSS, n=9, P50.05). In the presence of L-NMMA, propranolol had no additional e ect on large arteries, whereas in small arteries there was greater potentiation than for either agent alone (67.8+5.9% KPSS, n=4). 4 b-Adrenoceptor-mediated relaxation was examined in arteries constricted with prostaglandin F 2a (50 mM). In the presence of propranolol isoprenaline caused an unexpected vasoconstriction, which was abolished by phentolamine (10 mM). In the presence of phentolamine, isoprenaline caused a maximum relaxation of 43.3+2.1% (n=6) in large, and 49.0+4.5% (n=6) in small arteries. L-NMMA substantially reduced relaxation in large arteries (7.4+1.5%, n=6, P50.01), but was less e ective in small arteries (26.8+5.8, n=5, P50.05). 5 Atenolol (b 1 -antagonist, 5 mM) reduced relaxation to isoprenaline (large: 34.8+4.5%, n=5; small: 35.0+1.9%,n=6), but in combination with L-NMMA had no additional e ect over L-NMMA alone. ICI 118551 (b 2 -antagonist, 0.1 mM) reduced isoprenaline-induced relaxation more than atenolol (large: 18.0+4.6%, n=6, P50.05; small: 25.6+10.7%, n=6, P50.05). ICI 118551 in combination with L-NMMA substantially reduced relaxation (large: 4.8+2.6%, n=9; small: 6.5+3.6%, n=5). 6 Salbutamol-induced relaxation was reduced substantially by L-NMMA in large arteries (control: 34.7+6.4%, n=6; +L-NMMA: 8.3+1.3%, n=5, P50.01), but to a lesser extent in small arteries (control: 50.9+7.5%, n=6; +L-NMMA: 23.0+0.7%, n=5, P50.05). Relaxation to forskolin was also partially antagonized by L-NMMA. 7 These results suggest that the meagre vasoconstriction to noradrenaline in small pulmonary arteries is partially due to a greater b-adrenoceptor-mediated component than in large arteries. b-Mediated vasorelaxation in large arteries was largely NO-dependent, whereas in small arteries a signi®cant proportion was NO-independent. Noradrenaline stimulation was also asso...

show abstract

Section: Discussionsupporting

confidence: 53%

Noradrenaline, β‐adrenoceptor mediated vasorelaxation and nitric oxide in large and small pulmonary arteries of the rat

Priest¹,

Hucks²,

Ward³

1997

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…25,39 It has been shown to exert relaxant effects on vascular smooth muscle because of multiple actions such as affecting cellular Ca 2 þ homeostasis as a nonspecific calcium antagonist, enhancing NO synthesis or inhibiting the activity of phosphodiesterase leading to the subsequent enhancement of cAMP concentration. [40][41][42][43] This study was determined to explore its mechanism underlying the relaxatory actions of chuanxiongzine on corpus cavernosal smooth muscle. Our studies have shown that chuanxiongzine was effective in relaxing isolated rabbit cavernosal strips and depressing the response to PE in a concentration-dependent manner in vitro.…”

Section: Discussionmentioning

confidence: 99%

Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits

et al. 2009

View full text Add to dashboard Cite

It has been shown that there are many Chinese traditional herbals that can enhance sexual activity. Chuanxiongzine is a vasoactive ingredient that has been isolated and purified from Ligusticum chuanxiong Hort. In previous studies, it has been found that chuanxiongzine was effective in relaxing rabbit corpus cavernosum smooth muscle. We determined the effects of chuanxiongzine on relaxation of isolated corpus cavernosum strips in vitro and on increase of intracavernous pressure (ICP) in vivo in rabbits. Chuanxiongzine caused a concentration-dependent relaxation of phenylephrine precontracted isolated corpus cavernosum strips (EC 50 1.58 Â 10 À4 mol l À1 ), which were endothelium independent and NO independent. However, the guanylyl cyclase inhibitor 1-H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one significantly shifted the chuanxiongzine concentration-response relationship to the right. Although there was no significant difference in the level of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in isolated corpus cavernosum strips treated with chuanxiongzine or vehicle, chuanxiongzine caused a significant rise in the level of cGMP and cAMP in isolated corpus cavernosum strips pretreated with the activator of adenylyl cyclase forskolin and the source of NO sodium nitroprusside. In an in vivo study, chuanxiongzine dose-dependently raised ICP after the intracavernous injection of its cumulative doses (0.5, 1, 2 and 5 mg kg À1 ). The ICP increased from baseline to 19.1±3.7, 24.8±2.1, 30.2 ± 4.8 and 39.7 ± 6.1 mm Hg, respectively, and the duration of tumescence ranged from 8.5 ± 2.8 to 22.9 ± 7.3 min. Our results show that chuanxiongzine can relax isolated corpus cavernosum strips of rabbits in vitro and increase ICP of rabbits in vivo, which is neither endothelium dependent nor NO dependent, but may be partly mediated by the inhibition of cAMP phosphodiesterase or cGMP phosphodiesterase.

show abstract

“…Further experiments are required before this can be clari®ed, and indeed whether the lack of response in mesenteric arteries is common to other systemic artery types. It is notable that relaxation to another agent that increases cyclic AMP, the putative cyclic AMP speci®c PDE inhibitor tetramethylpyrazine (Lin et al, 1993), is also partially selective in the rat to pulmonary relative to mesenteric arteries (Peng et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Plane & Garland, 1996), and it has been suggested that stimulation of a 1 -adrenoceptors may potentiate relaxation to b-adrenoceptor agonists in pulmonary arteries (Peng et al, 1996;Priest et al, 1997). 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).…”

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

View full text Add to dashboard Cite

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.

show abstract

Ligustrazine‐induced endothelium‐dependent relaxation in pulmonary arteries via an NO‐mediated and exogenous L‐arginine‐dependent mechanism

Cited by 45 publications

References 19 publications

Noradrenaline, β‐adrenoceptor mediated vasorelaxation and nitric oxide in large and small pulmonary arteries of the rat

Noradrenaline, β‐adrenoceptor mediated vasorelaxation and nitric oxide in large and small pulmonary arteries of the rat

Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits

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

Contact Info

Product

Resources

About