Effects of maturation on mechanisms of cGMP-induced cerebral vasodilatation.
In light of observations that cerebrovascular levels of cGMP vary during maturation, the present study examines the possibility that the mechanisms mediating cGMP-induced cerebral vasodilatation also change during maturation. Specifically, these experiments explore age-related changes in the ability of cGMP to both: (1) depress cytosolic calcium concentration, and (2) attenuate contractile protein calcium sensitivity in alpha-toxin and beta-escin permeabilized preparations as well as fura-2 loaded arteries. The present data demonstrate that: (1) cGMP attenuates cytosolic calcium concentration at lower concentrations than required to reduce myofilament calcium sensitivity; (2) both potassium-induced and 5HT-induced contractions were more sensitive to cGMP in fetal than adult arteries; (3) all potassium-induced increases in cytosolic calcium were resistant to the effects of cGMP, but those produced by 5HT were sensitive to attenuation by cGMP, and more so in fetal than in adult basilar arteries, and (4) cGMP attenuated both basal and agonist-enhanced myofilament calcium sensitivity. Overall, these data demonstrate that the mechanisms mediating the multiple vasoactive effects of cGMP are more potent in immature than in mature cerebral arteries and are heavily influenced by both the artery type and the method of contraction.
Nauli
S M
SM
Department of Pharmacology, Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, Calif 92350, USA.
Williams
J M
JM
Pearce
W J
WJ
D000818:Animals; D001488:Basilar Artery / Q000254:growth & development / Q000502:physiology; D017536:Carotid Artery, Common / Q000254:growth & development / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000502:physiology; D005456:Fluorescent Dyes; D016257:Fura-2; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D012756:Sheep; D013873:Thionucleotides / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
C090860:8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D010975:Platelet Aggregation Inhibitors; D013873:Thionucleotides; D012701:Serotonin; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D006152:Cyclic GMP; D011188:Potassium; D016257:Fura-2