Characterization of changes in mechanical responses to histamine in omental resistance arteries in pre-eclampsia.
Changes in the effect of histamine on the smooth muscle of resistance arteries in pre-eclampsia were investigated by measuring isometric contractions in endothelium-denuded strips of omental resistance arteries from pre-eclamptic and normotensive pregnant women (pregnancy-term matched). Histamine (0.03 -1 microM) caused concentration-dependent relaxation of the contraction induced by 9, 11-epithio-11,12-methano-thromboxane A(2) (STA(2)) in strips from both groups. Sensitivity (for pre-eclampsia: pD(2)=6.66+/-0.04, n=5 and for normotensive pregnant women: pD(2)=7.07+/-0.03, n=10, P<0.001) was lower and the maximum response (90.6+/-0.6% vs 95.5+/-1.1%, P<0.05) was smaller in strips from pre-eclamptic women. Although 8-bromoadenosine-3', 5'-cyclic monophosphorothioate (Sp-isomer: Sp-8-Br-cAMPS, 0.1 - 0.3 mM), a phosphodiesterase (PDE)-resistant activator of adenosine-3',5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase, concentration-dependently attenuated the contraction induced by STA(2) in strips from both groups, the sensitivity (for pre-eclampsia: pD(2)=3.68+/-0.04, n=5 and for normotensive pregnant women: 3.94+/-0.09, n=7, P:=0.02) was lower and the maximum response (64.2+/-2.4% vs 74.9+/-4.4%, P:<0.05) was smaller in pre-eclampsia. In beta-escin-skinned strips, the pD(2) value for the contraction-inducing effect of Ca(2+) did not differ significantly between the two groups (for pre-eclampsia, n=6; for normotensive pregnant women, n=6). Thus, omental resistance arteries from human subjects with pre-eclampsia showed (i) a weaker H(2)-receptor-mediated relaxation to histamine and (ii) a weaker cyclic AMP-analogue-induced relaxation, suggesting that the reduced action of histamine may be partly due to a decreased effect of cyclic AMP.
Suzuki
Y
Y
Department of Obstetrics and Gynecology, Nagoya City University Medical School, Nagoya 467-8601, Japan.
Saitoh
M
M
Suzumori
K
K
Kajikuri
J
J
Itoh
T
T
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009852:Omentum / Q000098:blood supply; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects
D015124:8-Bromo Cyclic Adenosine Monophosphate; D013928:Thromboxane A2; C037866:STA 2; D006632:Histamine; D000242:Cyclic AMP; D002118:Calcium