Age-related changes in vascular responses: a review.

The effect of placental syncytiotrophoblast microvillous membranes from normal and pre-eclamptic women on the growth of endothelial cells in vitro

Pharmacology of adenosine receptors in the vasculature.

Endothelin and Ca++ agonist Bay K 8644: different vasoconstrictive properties.

The pathophysiology of the effects of cocaine on fetal development has been described along 2 major pathways: neurochemical effects and vasoconstrictive effects. Following a summary of these effects,

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Third pathophysiology of prenatal cocaine exposure.

1. The effect of different vasoactive agents on segments of human chorionic arteries and veins was analyzed. 2. The order of these agents to produce maximal contractile responses was: 5-hydroxytryptamine (5-HT) = histamine (H) = K+ greater than noradrenaline (NA) greater than or equal to phenylephrine (PHEN) greater than clonidine (CLON), and with regard to their potencies (EC50 values) was: 5-HT greater than or equal to NA greater than or equal to H greater than PHEN greater than CLON greater than K+. Dopamine and isoproterenol did not elicit any type of response. 3. The receptors involved on the contractions elicited by agonists were analyzed. 4. The results obtained suggest that: (1) 5-HT is the most potent vasoconstrictor agent of all those tested, whose effects appear to be mediated by 5-HT2- but not by alpha 1-adrenergic receptors; (2) chorionic vessels also possess H1-receptors; and (3) ketanserin has more affinity to block 5-HT2-receptors than to block alpha 1-adrenergic- and H1-receptors.

Actions of vasoactive drugs on human placental vascular smooth muscle.

1. 1. Adenosine induced concentration-dependent relaxations in segments of human chorionic arteries and veins precontracted with 75 mM K+, which were attenuated by l-methyl-3-isobutylxanthine (MIX). In the same conditions, l -phenylisopropyladenosine ( l -PIA), N-ethylcarboxamideadenosine (NECA) and dibutyryl-cyclic AMP (Db-cAMP) also produced concentration-dependent vasodilations. 2. 2. The order of potency with respect to EC50 was in arteries: NECA ⩾ l -PIA > Db-cAM P ⩾ adenosine, and in veins: l -PIA ⩾ NECA > adenosine ⩾ Db-cAMP. 3. 3. In segments precontracted with 10−6 M PGF2α, adenosine, NECA and l -PIA induced similar relaxations, which were markedly larger than those found in K+ contracted segments. 4. 4. Db-cAMP (15 min preincubation) inhibited more potently K+ (75 mM) contractions than adenosine. 5. 5. Adenosine reduced Ca addition-induced contractions in depolarized segments exposed to Ca-free medium, as well as 45Ca uptake elicited by 75 mM K+. 6. 6. It is concluded that there exists a similar population of adenosine A1 and A2 receptors in chorionic vessels, which mediate adenosine relaxation. This effect appears to be mainly produced by inhibition of Ca influx, but not by a cAMP-dependent mechanism.

Action of adenosine and characterization of adenosine receptors in human placental vasculature.

The effects of BAY-K-8644 on the contraction of cat middle cerebral and femoral arteries.

1. Effects of 5-hydroxytrypamine (5-HT) on cylindrical segments of human chorionic arteries and veins were investigated. Concentrations of 5-HT (up to 3 x 10(-6) M) produced concentration-dependent contractions; higher concentrations induced a reduction of the maximal response. These responses were antagonized by methysergide and ketanserin in a non-competitive manner. The contractions elicited by low 5-HT concentrations were more affected by methysergide (10(-7) M) than by ketanserin (10(-7) M). Ketanserin apparently increased the responses to high 5-HT concentrations in veins. Arteries appeared to be more sensitive to both drugs than veins. Single concentrations of 5-HT elicited transient contractions in both kinds of vessel. 2. Marked tachyphylaxis was seen in segments exposed to high concentrations of 5-HT or in which a concentration-response curve was determined. 3. Contractions induced by 5-HT were reduced in a Ca2+-free medium. Veins were more affected by the Ca2+ antagonists, nifedipine (10(-7) M), nicardipine (10(-5) M) and diltiazem (10(-5) M) than arteries. 4. 5-HT (10(-6) M) enhanced 45Ca2+ uptake in those vessels in which a concentration-response curve had not been previously determined. In veins, this increase was reduced by the three Ca2+ antagonists. 5. The results indicate that 5-HT responses in these vessels were greatly dependent on extracellular Ca2+. A type of 5-HT1-receptor may mediate responses to low 5-HT concentrations, while higher concentrations may activate 5-HT2-receptors. 5-HT may desensitize the latter by interconversion between a high affinity and low affinity state, as suggested by others, a change prevented in part by ketanserin.

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Effects of 5-hydroxytryptamine on human isolated placental chorionic arteries and veins.

5-Hydroxytryptamine (5-HT), noradrenaline (NA) and histamine induced concentration-dependent contractions in segments of human chorionic arteries and veins, whereas clonidine, an alpha 2-adrenoceptor agonist, had no effect. 5-HT and histamine induced strong contractions, while NA elicited weak contractions in some segments. The maximal response was similar for 5-HT and histamine. The order of potency (EC50 values) was: 5-HT greater than or equal to NA greater than or equal to histamine. These agonists induced tachyphylaxis, and single concentrations caused transient contractions. Contractions elicited by 5-HT were antagonized by ketanserin, a 5-HT2-receptor antagonist, which also antagonized the responses to NA and histamine, but at greater concentrations than those needed for 5-HT responses. Contractions elicited by histamine were reduced by diphenydramine. Low concentrations of 5-HT amplified contractions caused by NA and histamine. The results indicate that: (i) 5-HT is the most potent constrictor agent tested in these vessels; (ii) its effects are mediated by 5-HT2-receptors; and (iii) ketanserin at therapeutic plasma concentrations (10(-7) M) seems to block mainly 5-HT2-receptors, and alpha 1-adrenergic- and H1-receptors to a small extent only.

Jesús Reviriego

Papers

Actions of vasoactive drugs on human placental vascular smooth muscle.

Action of adenosine and characterization of adenosine receptors in human placental vasculature.

The effects of BAY-K-8644 on the contraction of cat middle cerebral and femoral arteries.

Effects of 5-hydroxytryptamine on human isolated placental chorionic arteries and veins.

Ability of ketanserin to block different receptors in human placental vessels.