Black women are at a greater risk to develop hypertension during pregnancy, with a 4.5 times higher rate of fatal preeclampsia than white women. Therefore, it is important to identify factors that may affect this risk. Our group previously proposed that high activity of the central regulatory enzyme of energy metabolism, creatine kinase (CK), may increase ATP-buffering capacity and lead to enhanced vascular contractility and reduced nitric oxide bioavailability. Therefore, we assessed microvascular contractility characteristics in isolated resistance arteries from self-defined black and white normotensive pregnant women using a Mulvany-Halpern myograph. Additionally, morphology was assessed with electron microscopy. Resistance-sized arteries obtained from omentum donated during cesarean sections (11 black women and 20 white women, mean age: 34 yr) studied in series showed similar morphology but significantly greater maximum contractions to norepinephrine (10(-5) M) in blacks [14.0 mN (1.8 SE)] compared with whites [8.9 mN (1.4 SE), P = 0.02]. Furthermore, we found greater residual contractility after the specific CK inhibitor dinitrofluorobenzene (10(-6) M) in black women [55% (6 SE)] compared with white women [28% (4 SE), P = 0.001] and attenuated vasodilation after bradykinin (10(-7) M) in black women [103% (6 SE)] compared with white women [84% (5 SE), P = 0.023], whereas responses to sodium nitroprusside (10(-4) M) and amlodipine (10(-6) M) were similar. We conclude that compared with white women, normotensive pregnant black women display greater resistance artery contractility and evidence of higher vascular CK activity with attenuated nitric oxide synthesis. These findings in normotensives may imply that the black population is at risk for a further incline in pregnancy-related hypertensive disorders.
"The guanidino compounds creatine and nitric oxide (NO) have a common precursor in L-Arginine . NO, RhoA/Rho kinase, and calcium-dependent pathways are intracellular effectors of blood pressure-regulating systems that converge on metabolic processes fueled by CK [11,12,72,88-91,93-95]. CK is high in persons of African ancestry [11,12,72,73], and this is thought to lead to greater contractility of vascular smooth muscle [11,12,72]. "
[Show abstract][Hide abstract] ABSTRACT: Background
Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy.
Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012.
We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited.
Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs.
BMC Medicine 05/2013; 11(1):141. DOI:10.1186/1741-7015-11-141 · 7.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Maternal psychosocial problems may affect fetal growth through maternal cortisol. This large prospective cohort study examined among 2810 women (1) the association of maternal cortisol levels with offspring birthweight and small for gestational age (SGA) risk and (2) the mediating role of maternal cortisol on the relation between maternal psychosocial problems and fetal growth. Pregnant women in Amsterdam were approached during their first prepartum visit (+/-13 weeks gestation). Total maternal cortisol level was determined in serum and maternal psychosocial indicators were collected through a questionnaire. Maternal cortisol levels were negatively related to offspring birthweight (B=-0.35; p<.001) and positively to SGA (OR=1.00; p=.027); after adjustment (for gestational age at birth, infant gender, ethnicity, maternal age, parity, BMI, and smoking), these effects were statistically insignificant. Post hoc analysis revealed a moderation effect by time of day: only in those women who provided a blood sample < or =09:00h (n=94), higher maternal cortisol levels were independently related to lower birthweights (B=-0.94; p=.025) and a higher SGA risk (OR=1.01; p=.032). Maternal psychosocial problems were not associated with cortisol levels. In conclusion, although an independent association between maternal cortisol levels in early pregnancy and offspring birthweight and SGA risk was not observed, exploratory post hoc analysis suggested that the association was moderated by time of day, such that the association was only present in the early morning. The hypothesis that maternal psychosocial problems affect fetal growth through elevated maternal cortisol levels could not be supported.
[Show abstract][Hide abstract] ABSTRACT: To explore whether 1) maternal depressive symptoms during pregnancy are associated with preterm birth (PTB), small for gestational age (SGA), a low Apgar score and child loss; 2) maternal smoking mediates the associations; and 3) the associations differ by ethnic background.
Pregnant women in Amsterdam were approached during their first prenatal visit to participate in the Amsterdam Born Children and their Development study. They filled out a questionnaire covering sociodemographic data, life-style, and (psychosocial) health. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale. The baseline sample consisted of 8,052 women; the main ethnic groups were: Dutch, Creole, Turkish, and Moroccan.
The prevalence of perinatal outcomes was: 5.4% (PTB); 12.3% (SGA); l 1.5% (low Apgar score); and 1.4% (child loss). The prevalence of high depressive symptomatology was 30.6%. After adjustment for maternal age, parity, education, ethnicity, prepregnancy body mass index, hypertension, alcohol and drug use, and a small mediation effect of maternal smoking, high versus low levels of depressive symptoms were associated with SGA (odds ratio [OR], 1.19; p = .02) and a low Apgar score (OR, 1.74; p = .01), but not with PTB (OR, 1.16; p = .18) and child loss (OR, 1.28; p = .24). Stratified analyses by ethnic background showed a tendency toward higher risks, although insignificant, among Creole women.
Several pathways may explain the detrimental effects of maternal depressive symptomatology on perinatal health outcomes, including a psychoendocrinological pathway involving the hormone cortisol or mediation effects by maternal risk behaviors. Further research should explore the underlying pathways, in particular among ethnic subgroups.
Psychosomatic Medicine 10/2010; 72(8):769-76. DOI:10.1097/PSY.0b013e3181ee4a62 · 3.47 Impact Factor
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