Effects of cyclic GMP elevation on isoprenaline‐induced increase in cyclic AMP and relaxation in rat aortic smooth muscle: role of phosphodiesterase 3

Delpy, Eric; Coste, Hervé; Gouville, Anne-Charlotte Le Monnier de

doi:10.1111/j.1476-5381.1996.tb15696.x

Cited by 80 publications

(63 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The proportion of NO-independent relaxation induced by isoprenaline in small pulmonary arteries was similar to that previously described in rat small mesenteric arteries (Graves & Poston, 1993). Our results are in clear agreement with previous studies on systemic arteries, that have suggested that isoprenaline-induced relaxation is at least partly dependent on NO and the endothelium (Gray & Marshall, 1992;Blankesteijn & Thien, 1993;Graves & Poston, 1993;Delpy et al, 1996).…”

Section: Discussionsupporting

confidence: 82%

“…However Graves & Poston (1993) showed a slight enhancement of forskolininduced relaxation in the presence of L-NAME in rat mesenteric arteries, and Kuhn et al (1991) were unable to demonstrate any increase in NO release from bovine cultured endothelial cells following experimental increases in cyclic AMP. Our results in pulmonary arteries are more similar to those of Delpy et al (1996) than Gray & Marshall (1992), in that the forskolin concentration-response curve was shifted to the right by L-NMMA, with no change in maximum relaxation. In direct contrast to the b-agonists examined in our preparation, forskolin was a more e ective vasodilator in large as opposed to small pulmonary arteries.…”

Section: Discussionsupporting

confidence: 72%

“…8-Bromo-cyclic GMP and activators of guanylate cyclase have been shown to potentiate the isoprenaline-induced rise in cyclic AMP and subsequent relaxation, and it has been suggested that the e ects of inhibition of NO synthesis on b-adrenoceptor mediated relaxation could be explained in terms of a reduction in basal NO, and hence loss of this potentiation (Maurice & Haslam, 1990;Lugnier & Komas, 1993;Delpy et al, 1996). In contrast Gray & Marshall (1992) have shown that L-NOARG abolishes the rise in smooth muscle cyclic GMP induced by isoprenaline without decreasing cyclic AMP.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas the classical view is that b-adrenoceptor-induced vasodilatation is mediated entirely via activation of adenylate cyclase in the smooth muscle, there are now several ®ndings suggesting that it may be, at least in part, endothelium dependent, as isoprenaline-induced relaxation in rat systemic arteries has been shown to be inhibited by removal of the endothelium or inhibition of NO synthesis (Gray & Marshall, 1992;Blankesteijn & Thien, 1993;Graves & Poston, 1993;Delpy et al, 1996), although the degree of inhibition obtained is variable. However, Moncada et al (1991) have shown that isoprenaline-induced relaxations in rat aorta are not endothelium-dependent, and Eckly et al (1994) showed no alteration of isoprenaline-induced changes in aortic smooth muscle adenosine 3':5'-cyclic monophosphate (cyclic AMP) or guanosine 3':5'-cyclic monophosphate (cyclic GMP) following removal of the endothelium.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Priest¹,

Hucks²,

Ward³

1997

British J Pharmacology

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: 82%

Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Priest¹,

Hucks²,

Ward³

1997

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…There is known to be signi®cant cross-talk between cyclic AMP and cyclic GMP pathways (Lincoln & Cornwell, 1993;Vigne et al, 1994), and activators of guanylate cyclase have been shown to potentiate isoprenaline stimulated cyclic AMP accumulation and relaxation in vascular smooth muscle (Maurice & Haslam, 1990;Delpy et al, 1996). However PE has also been shown to stimulate or potentiate accumulation of cyclic AMP directly in a variety of other cell types (Pedarzani & Storm, 1996;Traish et al, 1997;Ruan et al, 1998), although there are few reports on vascular smooth muscle (Izumi et al, 1996).…”

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

Therapeutic efficacy of milrinone in the management of enterovirus 71‐induced pulmonary edema

Wang

Lei

Huang

et al. 2005

Pediatric Pulmonology

View full text Add to dashboard Cite

Hand, foot, and mouth disease and herpangina are the major clinical manifestations of enterovirus 71 (EV71) infections. Brain-stem encephalitis and pulmonary edema are severe complications that can lead to death. This study was designed to evaluate the potential therapeutic effect of milrinone, a phosphodiesterase (PDE) inhibitor, in the treatment of patients with EV71-induced pulmonary edema. We conducted a historically controlled trial of 24 children with severe EV71-induced pulmonary edema from April 1998-June 2003 in southern Taiwan. Patients were divided into groups treated before and after the introduction of milrinone therapy. Etiological diagnosis was established by viral cultures and confirmed by specific immunofluorescence and neutralization tests. All 24 patients were below 5 years of age. The mortality was lower in the milrinone-treated vs. nontreated group (36.4% vs. 92.3%, P=0.005). Sympathetic tachycardia was decreased in patients treated with milrinone compared to controls (144 +/- 17/min vs. 206 +/- 26/min, P=0.004). A marked decrease in IL-13 (77 +/- 9 pg/ml vs. 162 +/- 88 pg/ml, P=0.001) was observed in milrinone-treated patients compared to controls. There was a significant reduction in white blood cell (10,838 +/- 4,537/mm3 vs. 19,475 +/- 7,798/mm3, P=0.009) and platelet (257 +/- 45 x 10(3)/mm3 vs. 400 +/- 87 x 10(3)/mm3, P=0.001) counts in milrinone-treated patients compared to controls. These results were associated with improvement in sympathetic regulation and decrease in IL-13 production. Milrinone therapy may provide a useful therapeutic approach for this highly lethal disorder.

show abstract

Effects of cyclic GMP elevation on isoprenaline‐induced increase in cyclic AMP and relaxation in rat aortic smooth muscle: role of phosphodiesterase 3

Cited by 80 publications

References 30 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

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

Therapeutic efficacy of milrinone in the management of enterovirus 71‐induced pulmonary edema

Contact Info

Product

Resources

About