Epinephrine only partially reverses histamine-induced vasodilation in human internal mammary arteries, whereas vasopressin, methylene blue, and drugs involved in the inhibition of nitric oxide and prostaglandin generation lead to a complete reversal of the vascular relaxation.

Purpose: Some anticholinesterases (anti-ChE) such as neostigmine and pyridostigmine but not edrophonium, stimulate phosphatidylinositol (PI) response. Although a direct relationship was suggested between the increase in PI response and airway smooth muscle contraction, there are no data regarding the effects of anti-ChE drugs on airway smooth muscle. Thus, we examined the contractile properties and PI responses produced by anti-thE drugs.Methods: Controctile response. Rat tracheal ring was suspended between two stainless hooks in Krebs-Henseleit Conclusions: The data suggest that anti-ChE drugs activate the M 3 receptors at the tracheal effector site. Objecdf : Certains anticholinest&asiques (anti-ChE) comme la nEostigmime et la pyridostigmine, mais non redrophonium, stimulent la r~ponse du phosphatidylinositol (PI). Bien qu'on air ~voqu~ une relation directe entre I'augmentation de la r~ponse PI et la contraction des muscles lisses du conduit a&ien, il n'y a pas de donn&s concernant les effets de m~dicaments anti-ChE sur les muscles {isses des voies a&iennes. Doric, nous avons &udi~ les propri&& contractiles et les r~ponses du PI produites par les m~dicaments anti-ChE.M&hode : R~ponse contractile. Des anneaux de trach& de rat ont &E suspendus entre des crochets inox dans une solution de Krebs-Henseleit (K-H). (I) Du carbachol (CCh), des m~dicaments anti-ChE (n~ostigmine, pyridostigmine, edrophonium) ou DMPP (un agoniste nicotinique ganglionnaire sfilectif) ont ~t~ ajout~s pour induire une contraction active. (2) Les effets du m~thobromide 4-diph~nylac&oxy-N-m~thyl-pip&idine (4-DAMP), un antagoniste des r&epteurs muscariniques M 3, sur la contraction d'anneaux de trach& de rat induite par la n~ostigmine ou la pyridos~igmine, ont ~t~ examines. R~sultats : Le carbachol (0, I A/M), la nEostigmine ( I AIM), la pyridostigmine (10/~M) mais non I'edrophonium ou le DMPP, ont cause des contraction des anneaux de trach&. La 4-DAMP, contrairement ~ la t&rodotoxine, a inhib~ les contractions induites par la nEostigmine et la pyridostigmine. I'accumulation d'lP, induite par la n~ostig-mine ou la pyridostigmine a &E inhib~e par la 4-DAMP. Conclusion : Les donn~es indiquent que les m~dicaments anti-ChE activent les r&epteurs M 3 au site effecteur de la trach~e.

We studied the effects of hydralazine, nicardipine, nitroglycerin, and fenoldopam (a dopamine D1-agonist) on isolated human umbilical arteries (HUA) from patients classified as normotensive and with pregnancy-induced hypertension (PIH). Umbilical artery rings were contracted with the thromboxane A(2) analog (U46619; 10(-8) M) and then exposed to cumulative concentrations of fenoldopam, hydralazine, nicardipine, and nitroglycerin. Second, rings were preexposed to prazosin (10(-5) M), phenoxybenzamine (10(-5) M), or none, and the constriction responses to increasing doses of fenoldopam or dopamine were recorded. Nitroglycerin, hydralazine, and nicardipine produced concentration-dependent relaxation of U46619-preconstricted HUA segments from normotensive and PIH patients. Fenoldopam and dopamine induced umbilical artery constriction in both normal and PIH rings at concentrations > or = 10(-5) M and > or = 10(-3) M, respectively. Phenoxybenzamine, but not prazosin, pretreatment irreversibly abolished fenoldopam-induced contraction. In this in vitro study, nitroglycerin was the most potent vasodilator of the HUA constricted with U46619, followed by nicardipine and hydralazine. However, fenoldopam constricted HUA rings only at supratherapeutic concentrations. No significant differences of vascular responses to fenoldopam (P = 0.3534), nitroglycerin (P = 0.7416), nicardipine (P = 0.0615), and hydralazine (P = 0.5514) between rings from normotensive or hypertensive pregnant patients were shown.

Various antihypertensive agents are effective in attenuating U46619-induced IMA vasoconstriction, but the efficacy and potency differ. The in vitro vasodilation may not be simply extrapolated to the clinical efficacy or outcome of each antihypertensive therapy; however, our data provide additional grounds for the choice of antihypertensive medication. Further clinical studies are needed to help to fully elucidate the use of different antihypertensive agents and clinical outcomes.