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Purinoceptor‐mediated contractility of the perfused uterine vasculature of the guinea‐pig: influence of oestradiol and pregnancy
Author(s) -
Haynes John M,
Pennefather Jocelyn N,
Sikorski Bogdan
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03839.x
Subject(s) - vasoconstriction , endocrinology , phenylephrine , medicine , guinea pig , agonist , biology , uridine triphosphate , uterus , pharmacology , receptor , nucleotide , biochemistry , gene , blood pressure
Summary 1. The effects of ATP, the stable ATP analogues α,β‐methylene ATP (α,β‐mATP), 2‐methylthioATP (2meSATP) and adenosine tetraphosphate (ATP 4 ), the pyrimidine nucleotide uridine 5′‐triphosphate (UTP) and the α 1 ‐adrenoceptor agonist phenylephrine were examined on the isolated perfused uterine vasculature of dioestrous, oestradiol‐treated, dexamethasone‐treated and late‐pregnant guinea‐pigs. 2. The α 1 ‐adrenoceptor agonist phenylephrine elicited concentration‐dependent vasoconstriction from preparations of perfused uterine vasculature from dioestrous, estradiol‐treated and late‐pregnant guinea‐pigs. The mean maximal response to phenylephrine was unaffected by treatment of dioestrus guinea‐pigs with oestradiol or dexamethasone, but was reduced in preparations from late‐pregnant animals. 3. In perfused uterine arteries from dioestrous animals, the pyrimidine UTP, but not ATP 4 and ATP, elicited vasoconstrictor responses. In preparations from oestradiol‐treated animals, all three agonists elicited vasoconstriction, with a rank order of potency of ATP 4 = UTP ≫ ATP, whereas in preparations from late‐pregnant animals this order of potency was ATP 4 ≫ UTP = ATP. In preparations from dexamethasone‐treated animals, the vasoconstriction was similar to that seen in dioestrous animals. Vasoconstrictor responses to ATP 4 were significantly greater in preparations of uterine vasculature from oestradiol‐treated and pregnant animals than in preparations from dioestrous animals or dexamethasone‐treated animals. 4. In preparations from dioestrous, oestradiol‐treated, pregnant and dexamethasone‐treated animals, α,β‐mATP was approximately two to three orders of magnitude more potent than 2meSATP. Compared with preparations from dioestrous animals, the maximal responses to α,β‐mATP were significantly greater in tissues from oestradiol‐treated and pregnant animals. In preparations from dioestrous animals, the P2 purinoceptor antagonist suramin (100 µmol/L) inhibited the responses to α,β‐mATP, but not those to ATP 4 . 5. The present study has demonstrated that pregnancy, but not the steroid treatment of dioestrous guinea‐pigs with oestradiol or dexamethasone, reduces the sensitivity of the guinea‐pig isolated perfused uterine vasculature to phenylephrine. In contrast, preparations from pregnant or oestradiol‐treated guinea‐pigs respond to ATP 4 and to α,β‐mATP with significantly greater constrictions than those of dioestrous or dexamethasone‐treated animals. These data indicate that the sensitivity of the uterine vasculature to adrenoceptor and purinoceptor agonists is differentially regulated by oestradiol and pregnancy, but not by the synthetic glucocorticoid dexamethasone.