Increased concentration of circulating calcitonin gene related peptide during normal human pregnancy.

Stevenson, John C.; Macdonald, David W.; Warren, Richard; Booker, Michael; Whitehead, Malcolm

doi:10.1136/bmj.293.6558.1329

Cited by 129 publications

(59 citation statements)

References 16 publications

(3 reference statements)

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“…It has been reported that both estrogen and progesterone, which are ovarian hormones, stimulate CGRP peptide synthesis in dorsal root ganglia neurons through increasing CGRP mRNA (Gangula et al 2000a). Plasma CGRP levels in rats and humans have been reported to increase with pregnancy and decrease postpartum (Stevenson et al 1986, Saggese et al 1990, Gangula et al 2000b. These findings suggest that ovarian hormones may be responsible for increased CGRP levels in the circulation.…”

Section: Discussionmentioning

confidence: 53%

Up-regulation of calcitonin gene-related peptide receptors underlying elevation of skin temperature in ovariectomized rats

Noguchi

Ikarashi²,

Yuzurihara³

et al. 2002

Journal of Endocrinology

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We investigated the mechanism for the augmentation of the calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature in ovariectomized (OVX) rats. I.v. injection of CGRP (10 µg/kg) elevated skin temperature of the hind paws. The elevation was significantly greater in OVX rats than in sham-operated rats and was inhibited by pretreatment with human CGRP (100-1000 µg/kg i.v.), a CGRP receptor antagonist, in a dose-dependent manner. In addition, ovariectomy not only potentiated vasorelaxation due to CGRP but increased the number of CGRP receptors in mesenteric arteries. Further, the plasma concentration of endogenous CGRP was significantly lower in OVX rats. These results suggest that the low concentration of plasma CGRP due to ovarian hormone deficiency may induce the increase in the number of CGRP receptors due to up-regulation. Therefore, the increased number of CGRP receptors may be responsible for potentiation of exogenous CGRPinduced elevation of skin temperature in OVX rats. The mechanism underlying the hot flashes observed in menopausal women may also involve, in part, the up-regulation of CGRP receptors following ovarian hormone deficiency.

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Section: Discussionmentioning

confidence: 53%

Up-regulation of calcitonin gene-related peptide receptors underlying elevation of skin temperature in ovariectomized rats

Noguchi

Ikarashi²,

Yuzurihara³

et al. 2002

Journal of Endocrinology

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“…PlGF may play a role especially after the first trimester, when serum concentration begins to rise as the placenta grows and matures (115). Another candidate is calcitonin gene-related peptide (CGRP), which increases in the blood during early pregnancy in women (183). CGRP is a potent vasodilator (187), and therefore, it may contribute to systemic and renal vasodilation of pregnancy.…”

Section: Molecular Mechanisms Of Renal Vasodilation In Pregnancymentioning

confidence: 99%

The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?

Conrad

Davison

2014

American Journal of Physiology-Renal Physiology

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Conrad KP, Davison JM. The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?. Am J Physiol Renal Physiol 306: F1121-F1135, 2014. First published March 19, 2014 doi:10.1152/ajprenal.00042.2014.-During the first trimester of human pregnancy, the maternal systemic circulation undergoes remarkable vasodilation. The kidneys participate in this vasodilatory response resulting in marked increases in renal plasma flow (RPF) and glomerular filtration rate (GFR). Comparable circulatory adaptations are observed in conscious gravid rats. Administration of the corpus luteal hormone relaxin (RLN) to nonpregnant rats and humans elicits vasodilatory changes like those of pregnancy. Systemic and renal vasodilation are compromised in midterm pregnant rats by neutralization or elimination of circulating RLN and in women conceiving with donor eggs who lack a corpus luteum and circulating RLN. Although RLN exerts both rapid (minutes) and sustained (hours to days) vasodilatory actions through different molecular mechanisms, a final common pathway is endothelial nitric oxide. In preeclampsia (PE), maternal systemic and renal vasoconstriction leads to hypertension and modest reduction in GFR exceeding that of RPF. Elevated level of circulating soluble vascular endothelial growth factor receptor-1 arising from the placenta is implicated in the hypertension and disruption of glomerular fenestrae and barrier function, the former causing reduced K f and the latter proteinuria. Additional pathogenic factors are discussed. Last, potential clinical ramifications include RLN replacement in women conceiving with donor eggs and its therapeutic use in PE. Another goal has been to apply knowledge gained from investigating circulatory adaptations in pregnancy toward identifying and developing novel therapeutic strategies for renal and cardiovascular disease in the nonpregnant population. So far, one candidate to emerge is RLN and its potential therapeutic use in heart failure. renal hemodynamics; glomerular filtration; osmoregulation; relaxin; nitric oxide; assisted reproductive technology; glomerular endotheliosis; soluble vascular endothelial growth factor receptor-1; heart failure Renal Plasma Flow and Glomerular Filtration in Normal PregnancyMARKED VASODILATION OF THE MATERNAL CIRCULATION occurs in the first trimester of human pregnancy. Consequently, there is a precipitous and profound decline in systemic vascular resistance (SVR) that in turn abets a reciprocal increase in cardiac output (CO) of ϳ40% or 2 l/min lasting throughout pregnancy (23,163). Vasodilation of nonreproductive organs like the kidneys accounts mostly for the early gestational fall in SVR and rise in CO. The fall in SVR is nearly offset by the rise in CO; hence, mean arterial pressure (MAP) declines, but only modestly, by 5-10 mmHg (23,38,163). Although counterintuitive, this metamorphosis of the maternal circulation is virtually complete by the end of the first or beginning of the second trimester, when fetal crown rump length and place...

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“…Furthermore, CGRP-containing nerve fibers are present in the human uterus (7), and CGRP relaxes contractile activity in the human uterus and fallopian tubes (7). CGRP is also present in the circulation, and the plasma levels of this neuropeptide are increased during human pregnancy (5,20), indicating that CGRP may play a role in the regulation of human myometrial contractility during pregnancy and labor. We examined the in vitro relaxant effects of CGRP on human myometrium using concentrations of CGRP from 10 -11 to 10 -6 M, based upon the physiologic concentration of circulatory CGRP in humans (10 -10 M; refs.…”

Section: Discussionmentioning

confidence: 99%

Involvement of calcitonin gene–related peptide in the modulation of human myometrial contractility during pregnancy

Dong¹,

Li²,

Kondapaka³

et al. 1999

J. Clin. Invest.

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IntroductionUterine quiescence is a requirement for the successful completion of term gestation. Failure to maintain uterine relaxation often results in preterm deliveryone of the leading causes of infant mortality and morbidity. Studies have shown that the quiescent state of the myometrium is maintained not only by absence or low levels of stimulatory factors, such as oxytocin receptors (1), gap junction channels (2), and α-adrenergic receptors (3), but also by an enhancement of inhibitory factors, including nitric oxide (4). However, little research has been done to define the mechanisms that maintain myometrial relaxation during pregnancy, compared with research on those mechanisms that promote the onset of labor.Calcitonin gene-related peptide (CGRP) is a 37-residue neuropeptide that results from tissue-specific alternative splicing of the primary RNA transcript of the calcitonin/CGRP gene (5). The vasodilator effects of CGRP have been demonstrated in the human fetalplacental circulation (6). With immunocytochemical techniques, CGRP-immunoreactive nerve fibers were found in rat and human uterus (7,8); CGRP relaxes contractile activity of the uterus in rats and humans (7,8). Therefore, CGRP is proposed to be a modulator of myometrial contractility during gestation. This study investigated whether uterine relaxation responses to CGRP are differentially regulated in humans during pregnancy and labor, and if the actions of CGRP are mediated by changes in CGRP receptors (CGRP-Rs). MethodsHuman subjects. The medical procedures and the process of consent for this study were approved by the Institutional Review Board of the University of Texas Medical Branch (UTMB). All human subjects, who were patients admitted to UTMB, were either women undergoing cesarean sections or nonpregnant women having hysterectomies. All provided written informed consent. Information on each subject regarding dates of pregnancy, number of pregnancies, age, prior drug treatment, and uterine contractions was collected and stored in a computerized database for later review. Specimens from each subject were taken from the lower uterine segment at the site of incision through the uterine wall. A specimen of approximately 2.0 × 0.6 × 0.6 cm was collected and divided into smaller portions (1.0 × 0.2 × 0.2 cm). Once each tissue sample was collected, it was assigned a number to blind the sample and to ensure confidentiality. Received for publication January 20, 1999, and accepted in revised form July 29, 1999.Calcitonin gene-related peptide (CGRP) is a potent vasodilator and relaxes smooth muscle of a variety of tissues, but the effects of CGRP on human myometrial contractions and the changes in CGRP receptors (CGRP-Rs) in human myometrium have not been described. We report that CGRP induced dose-dependent relaxation in spontaneously contracting myometrium from pregnant women. This relaxation effect is diminished in myometrium obtained from patients during labor and in the nonpregnant state. CGRP-induced relaxations are inhibited by a CGRP-R antago...

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Increased concentration of circulating calcitonin gene related peptide during normal human pregnancy.

Cited by 129 publications

References 16 publications

Up-regulation of calcitonin gene-related peptide receptors underlying elevation of skin temperature in ovariectomized rats

Up-regulation of calcitonin gene-related peptide receptors underlying elevation of skin temperature in ovariectomized rats

The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?

Involvement of calcitonin gene–related peptide in the modulation of human myometrial contractility during pregnancy

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