Calcium entry blockade as a therapeutic principle in the female urogenital tract

Forman, Axel

doi:10.3109/00016348409156969

Cited by 10 publications

(4 citation statements)

References 132 publications

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“…In the myometrial smooth muscle preparations, spontaneous contractions and contractions induced by K + . oxytocin and PGFzD were abolished in Cat+free medium, confirming previous results (Forman 1984). These responses were also effectively reduccd by nitrcndipinc.…”

supporting

confidence: 90%

“…The present results suggest that even if these agents act on intracellulary stored calcium, transmembrane calcium influx sensitive to calcium channel blockers is a necessary step in the excitation-contraction coupling. This implies that these drugs may have clinically useful relaxant effects on the human myometrium, as also suggested by in vivo studies (Forman et al 1982;Forman 1984). Effects on foetal placental vascular resistance and haemodynamics constitue an important aspect of antihypertensive treatment in pregnancy.…”

mentioning

confidence: 80%

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Inhibitory Effects of Nitrendipine on Myometrial and Vascular Smooth Muscle in Human Pregnant Uterus and Placenta

Maigaard

Forman

Brogaard‐Hansen

et al. 1986

Acta Pharmacologica et Toxicologica

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Human myometrial visceral and vascular preparations and placental chorionic and stem villous vessels were dissected from myometrial and placental specimens obtained at term Caesarean section and after vaginal delivery. Vascular ring preparations and myometrial strips were mounted in organ bath and isometric tension recorded. Only myometrial preparations developed spontaneous contractile activity, which was effectively blocked by the calcium channel blocker nitrendipine (NTD) 10−7M. Pretreatment with calcium‐depleted medium for 30 min. almost abolished myometrial responses to high K+ (124 mmol), oxytocin (OX) and prostaglandin F2a (PGF2a). Vascular responses to high K+ (124 mmol) were also nearly abolished by such treatment. However, noradrenaline (NA), vasopressin (VP) and PGF2a in myometrial arteries and PGF2a in chorionic vessels and stem villous arteries induced significant, but reduced contractions after calcium depletion. In all vascular preparations, exposed to calcium‐depleted medium, NTD (10−8M) almost abolished contractions induced by calcium (0.1–4.0 mM) in the presence of K+ (124 mmol) and depressed responses to calcium in the presence of the other agonists tested. NTD (10−10–10−7M) depressed myometrial contractions induced by K+, OX and PGF2a more effective than vascular responses to K+, NA, VP and PGF2a in the myometrial arteries and K+ and PGF2a in the placental arteries. It is concluded that activation of contraction in vessels from the human utero‐placental unit implies multiple cellular sources of calcium, while in myometrial smooth muscle, influx of superficially bound calcium may be an important initial step in contractile activation. Treatment with calcium channel blockers during late human pregnancy might involve relaxation of the myometrium together with vasodilatation of the myometrial and foetal placental vascular beds.

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supporting

confidence: 90%

mentioning

confidence: 80%

Inhibitory Effects of Nitrendipine on Myometrial and Vascular Smooth Muscle in Human Pregnant Uterus and Placenta

Maigaard

Forman

Brogaard‐Hansen

et al. 1986

Acta Pharmacologica et Toxicologica

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“…The effects of substance P and human CGRP on intracervical arteries did not seem to involve local prostaglandin synthesis, cholinoceptors or (1-adrencrgic re ceptors, as the relaxing responses seemed unaffected by indomethacin, atropine and propranolol. This is in line with studies on the effects of substance P in, for example, human oviductal arteries [15], and with in vestigations on CGRP-induced relaxation of cerebral arteries from the cat [16].…”

Section: Discussionsupporting

confidence: 68%

Effects of Human Calcitonin Gene-Related Peptide and Substance P on Human Intracervical Arteries

Hansen

Schifter

Allen

et al. 1988

Gynecol Obstet Invest

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The contractile effects of substance P and human calcitonin gene-related peptide (human CGRP) on isolated human intracervical arteries were studied. Human cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 14) and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. Neither compound affected resting tension. Both peptides showed potent relaxing effects on vessels precontracted by noradrenaline 10^––5M. Substance P exhibited the higher potency, while human CGRP showed the higher efficacy. The relaxing effects of the two compounds were unaffected by pretreatment with indomethacin 10^––6M, propranolol 10^––6M and atropine 10^––6M. The results support a role for the two peptides in the regulation of cervical blood flow.

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“…There are reasons to believe that several of the hormonal regulators of uterine motility activate the myometrium by increasing the influx of calcium from the extracellular medium (see , Forman et al 1981;Forman 1984). Even if extracellular calcium probably is not the only source of calcium used for myometrial activation, it could be expected that calcium entry blockers reduce myometrial contractility.…”

Section: Uterine Iiyporuclisitymentioning

confidence: 99%

Some Extracardiac Effects of Diltiazem and Other Calcium Entry Blockers

Andersson

1985

Acta Pharmacologica et Toxicologica

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Calcium entry blockers have a well documented relaxing effect of smooth muscle, vascular as well as non‐vascular. Mainly as a consequence of this action, the drugs have been used for treatment of several non‐cardiac disorders where hyperactivity of smooth muscle is considered to have an important role in the pathogenesis. In this short review some of these extracardiac effects of calcium entry blockers are discussed and also their clinical application.

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Calcium entry blockade as a therapeutic principle in the female urogenital tract

Cited by 10 publications

References 132 publications

Inhibitory Effects of Nitrendipine on Myometrial and Vascular Smooth Muscle in Human Pregnant Uterus and Placenta

Inhibitory Effects of Nitrendipine on Myometrial and Vascular Smooth Muscle in Human Pregnant Uterus and Placenta

Effects of Human Calcitonin Gene-Related Peptide and Substance P on Human Intracervical Arteries

Some Extracardiac Effects of Diltiazem and Other Calcium Entry Blockers

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