Tags

Type your tag names separated by a space and hit enter

Differential effects of phosphodiesterase PDE-3/PDE-4-specific inhibitors on vasoconstriction and cAMP-dependent vasorelaxation following balloon angioplasty.
Am J Physiol Heart Circ Physiol. 2007 Jun; 292(6):H2973-81.AJ

Abstract

It is known that cAMP and cGMP are important for vasorelaxation, and cyclic nucleotide phosphodiesterases (PDEs) regulate their levels. Balloon angioplasty (BAL) is associated with reduced cAMP and cGMP levels, and inhibition of PDE-3 reduces restenosis. In this study, we found that BAL increased PDE-3 activity, which affected vasoreactivity of rat aortic rings 24-h post-BAL; these were compared with intact (INT) and ex vivo endothelium-denuded rings (RUB) from sham rats. In BAL and RUB rings, vasorelaxant responses to ACh were abolished. The EC(50) for phenylephrine (PE) was 1.8-fold less in RUB than in INT or BAL, whereas the maximal contractile effect of PE was greater in BAL than in INT or RUB. PDE-3 inhibitors reduced the maximal response to PE by >65% in BAL compared with 10-30% in INT and RUB; the reduction of the maximal response to U-46619 was 37% in BAL compared with 8% in INT with no reduction in RUB. PDE-4 inhibitors reduced PE-induced tone by <30% in an endothelium-dependent manner. Vasorelaxant responses to agonists that utilize cAMP were greatly impaired in BAL and RUB rings, and inhibition of PDE-3 enhanced the vasorelaxant responses in BAL or RUB. Inhibition of PDE-4 increased vasorelaxant responses to isoproterenol (ISO) to a much lesser degree. Thus PDE-3 and PDE-4 inhibitors exhibited differential effects on PE-induced tone and vasorelaxant responses to ISO. Inhibition of PDE-3 also produced a greater increase in cAMP in BAL than INT or RUB rings. These results suggest that increased PDE-3 activity after BAL may promote a vasospastic state and that the reduction in cAMP may, possibly, influence vessel remodeling.

Authors+Show Affiliations

Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA. hong_zhao@nymc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17293498

Citation

Zhao, Hong, et al. "Differential Effects of Phosphodiesterase PDE-3/PDE-4-specific Inhibitors On Vasoconstriction and cAMP-dependent Vasorelaxation Following Balloon Angioplasty." American Journal of Physiology. Heart and Circulatory Physiology, vol. 292, no. 6, 2007, pp. H2973-81.
Zhao H, Quilley J, Montrose DC, et al. Differential effects of phosphodiesterase PDE-3/PDE-4-specific inhibitors on vasoconstriction and cAMP-dependent vasorelaxation following balloon angioplasty. Am J Physiol Heart Circ Physiol. 2007;292(6):H2973-81.
Zhao, H., Quilley, J., Montrose, D. C., Rajagopalan, S., Guan, Q., & Smith, C. J. (2007). Differential effects of phosphodiesterase PDE-3/PDE-4-specific inhibitors on vasoconstriction and cAMP-dependent vasorelaxation following balloon angioplasty. American Journal of Physiology. Heart and Circulatory Physiology, 292(6), H2973-81.
Zhao H, et al. Differential Effects of Phosphodiesterase PDE-3/PDE-4-specific Inhibitors On Vasoconstriction and cAMP-dependent Vasorelaxation Following Balloon Angioplasty. Am J Physiol Heart Circ Physiol. 2007;292(6):H2973-81. PubMed PMID: 17293498.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential effects of phosphodiesterase PDE-3/PDE-4-specific inhibitors on vasoconstriction and cAMP-dependent vasorelaxation following balloon angioplasty. AU - Zhao,Hong, AU - Quilley,John, AU - Montrose,David C, AU - Rajagopalan,Swarna, AU - Guan,Qizhi, AU - Smith,Carolyn J, Y1 - 2007/02/09/ PY - 2007/2/13/pubmed PY - 2007/8/3/medline PY - 2007/2/13/entrez SP - H2973 EP - 81 JF - American journal of physiology. Heart and circulatory physiology JO - Am J Physiol Heart Circ Physiol VL - 292 IS - 6 N2 - It is known that cAMP and cGMP are important for vasorelaxation, and cyclic nucleotide phosphodiesterases (PDEs) regulate their levels. Balloon angioplasty (BAL) is associated with reduced cAMP and cGMP levels, and inhibition of PDE-3 reduces restenosis. In this study, we found that BAL increased PDE-3 activity, which affected vasoreactivity of rat aortic rings 24-h post-BAL; these were compared with intact (INT) and ex vivo endothelium-denuded rings (RUB) from sham rats. In BAL and RUB rings, vasorelaxant responses to ACh were abolished. The EC(50) for phenylephrine (PE) was 1.8-fold less in RUB than in INT or BAL, whereas the maximal contractile effect of PE was greater in BAL than in INT or RUB. PDE-3 inhibitors reduced the maximal response to PE by >65% in BAL compared with 10-30% in INT and RUB; the reduction of the maximal response to U-46619 was 37% in BAL compared with 8% in INT with no reduction in RUB. PDE-4 inhibitors reduced PE-induced tone by <30% in an endothelium-dependent manner. Vasorelaxant responses to agonists that utilize cAMP were greatly impaired in BAL and RUB rings, and inhibition of PDE-3 enhanced the vasorelaxant responses in BAL or RUB. Inhibition of PDE-4 increased vasorelaxant responses to isoproterenol (ISO) to a much lesser degree. Thus PDE-3 and PDE-4 inhibitors exhibited differential effects on PE-induced tone and vasorelaxant responses to ISO. Inhibition of PDE-3 also produced a greater increase in cAMP in BAL than INT or RUB rings. These results suggest that increased PDE-3 activity after BAL may promote a vasospastic state and that the reduction in cAMP may, possibly, influence vessel remodeling. SN - 0363-6135 UR - https://www.unboundmedicine.com/medline/citation/17293498/Differential_effects_of_phosphodiesterase_PDE_3/PDE_4_specific_inhibitors_on_vasoconstriction_and_cAMP_dependent_vasorelaxation_following_balloon_angioplasty_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.00419.2006?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -