Identification, Characterization, and Functional Role of Phosphodiesterase Type IV in Cerebral Vessels: Effects of Selective Phosphodiesterase Inhibitors

Willette, Robert N.; Shiloh, Aaron O.; Sauermelch, Charles F.; Sulpizio, Anthony C.; Michell, Marcus P.; Cieslinski, Lenora B.; Torphy, Theodore J.; Ohlstein, Eliot H.

doi:10.1097/00004647-199702000-00011

Cited by 44 publications

(20 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have also shown the dilatory effects of dipyridamole as more or less selective phosphodiesterase inhibitors on intact cerebral arteries (Harris et al, 1989;Cosentino et al, 1992;Parfenova et al, 1993;Rosenblum et al, 1993;Willette et al, 1997). The present study demonstrated that dipyridamole induced only small changes in [Ca 2+ ]i in testicular or cerebral arteriole smooth muscle cells, and no dilation was observed in these arterioles.…”

Section: Response Of Smooth Muscle Cells In Testicular and Cerebral Asupporting

confidence: 67%

Dipyridamole inhibits intracellular calcium transients in isolated rat arteriole smooth muscle cells

Saino

Misaki

Matsuura

et al. 2008

Archives of Histology and Cytology

View full text Add to dashboard Cite

Section: Response Of Smooth Muscle Cells In Testicular and Cerebral Asupporting

confidence: 67%

Dipyridamole inhibits intracellular calcium transients in isolated rat arteriole smooth muscle cells

Saino

Misaki

Matsuura

et al. 2008

Archives of Histology and Cytology

View full text Add to dashboard Cite

“…Denbufylline-induced relaxation in vitro was also significantly impaired in basilar arteries obtained from a model of chronic vasospasm. In conclusion, PDE4 appears to be the predominant isozyme regulating vascular tone via cAMP hydrolysis in cerebral vessels (Willette et al, 1997). Further investigation is needed to determine whether inhibition of PDEs activity might be a useful approach in patients with SAH.…”

Section: Subarachnoid Hemorrhagementioning

confidence: 95%

Phosphodiesterases in the Vascular System.

Matsumoto

Kobayashi

Kamata

2003

J. Smooth Muscle Res.

View full text Add to dashboard Cite

Cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) are second messengers involved in the intracellular signal transduction of a variety of extracellular stimuli in several tissues. In the vascular system, these nucleotides play important roles in the regulation of vascular tone and in the maintenance of the mature contractile phenotype in smooth muscle cells. Given that cyclic nucleotide signaling regulates a wide variety of cellular functions, it is not surprising that cyclic nucleotide phosphodiesterases (PDEs). In paticular, the accumulating data showing that there are a large number of different PDE isozymes have triggered an equally large increase in interest about these enzymes. At least 11 different gene families of PDEs are currently known to exist in mammalian tissues. Most families contain several distinct genes, and many of these genes are expressed in different tissues as functionally unique alternative splice variants. This article reviews many of the important aspects about the structure, cellular localization, and regulation of each family of PDEs. Particular emphasis is placed on new information obtained in the last few years about vascular disease. The development of novel methods to deliver more potent and selective PDE inhibitors to individual cell types and subcellular locations will lead to new therapeutic uses for this class of drugs in diseases of the vascular system.

show abstract

“…numerous mechanisms have been proposed (Delgado et a!., 1988;Edwards et a!., 1992;Svendgaard et a!., 1987;Well urn et a!., 1985;Willette et a!., 1997).…”

mentioning

confidence: 99%

Acute Decrease in Cerebral Nitric Oxide Levels after Subarachnoid Hemorrhage

Sehba

Schwartz

Chereshnev

et al. 2000

J Cereb Blood Flow Metab

132

View full text Add to dashboard Cite

Summary: Disturbances in the nitric oxide (NO) vasodilatory pathway have been implicated in acute vasoconstriction and ischemia after subarachnoid hemorrhage (SAH). The authors hypothesize that blood released during SAH leads to vasocon striction by scavenging NO and limiting its availability. This was tested by measuring the major NO metabolites nitrite and nitrate in five different brain regions before and after experi mental SAH. The basal NO metabolites levels were as follows (mean ± SO, f.Lmol/mg wet weight): brain stem, 0.14 ± 0.07; cerebellum, 0.12 ± 0.08; ventral convexity cortex, 0.22 ± 0.15; dorsal convexity cortex, 0.16 ± 0.11; and hippocampus, 0.26 ± 0.17. In sham-operated animals, no effect of the nitric oxide synthase (NOS) inhibitor L G -nitro-L-arginine-methyl-ester (30 mg/kg) was found on NO metabolites 40 minutes after admin istration, but a significant decrease was seen after 120 minutes.Cerebral blood flow decreases acutely and ischemic injury occurs after subarachnoid hemorrhage (SAH) in both experimental and clinical studies. Cerebral arteries have been shown to respond to SAH with a biphasic constriction. An acute constriction begins minutes after the bleed, and delayed vasospasm begins 48 hours later . Although the significance of de layed vasospasm is recognized (Sobey and Faraci, 1998 604The NO metabolites decreased significantly 10 minutes after SAH in all brain regions except for hippocampus, and recov ered to control levels in cerebellum at 60 minutes and in brain stem and dorsal cerebral cortex 180 minutes after SAH, while remaining low in ventral convexity cortex. Nitrite recovered completely in all brain regions at 180 minutes after SAH, whereas nitrate remained decreased in brain stem and ventral convexity cortex. Our results indicate that SAH causes acute decreases in cerebral NO levels by a mechanism other than NOS inhibition and provide further support for the hypothesis that alterations in the NO vasodilatory pathway contribute di rectly to the ischemic insult after SAH.

show abstract

Identification, Characterization, and Functional Role of Phosphodiesterase Type IV in Cerebral Vessels: Effects of Selective Phosphodiesterase Inhibitors

Cited by 44 publications

References 23 publications

Dipyridamole inhibits intracellular calcium transients in isolated rat arteriole smooth muscle cells

Dipyridamole inhibits intracellular calcium transients in isolated rat arteriole smooth muscle cells

Phosphodiesterases in the Vascular System.

Acute Decrease in Cerebral Nitric Oxide Levels after Subarachnoid Hemorrhage

Contact Info

Product

Resources

About