Ethnic differences in resistance artery contractility of normotensive pregnant women.
ABSTRACT 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.
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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 beta-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. METHODS: 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. RESULTS: 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 beta-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. CONCLUSION: 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. · 7.28 Impact Factor
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ABSTRACT: The occurrence of common pregnancy-related medical disorders identifies women at high-risk of developing future vascular disease. Systematic reviews of cohort studies demonstrate that gestational diabetes confers a 7-fold risk increase for type 2 diabetes, while preeclampsia confers a 1.8-fold risk increase for type 2 diabetes and 3.4-fold risk increase for hypertension. Both gestational diabetes and hypertensive disorders of pregnancy (HDP) increase the risk of premature vascular disease, but the two-fold risk increase associated with preeclampsia is only partially explained by the development of traditional vascular risk factors. Despite the compelling evidence for gestational diabetes and HDP as vascular risk indicators, there are no published Canadian vascular prevention guidelines that recognize these postpartum women. In contrast, the 2011 American Heart Association guidelines on cardiovascular disease in women include gestational diabetes and HDP in their vascular risk assessment. Studies indicate that the importance of post-pregnancy surveillance of vascular risk factors in these women is underappreciated by both the women themselves and their physicians. Although a prudent diet and physically-active lifestyle were demonstrated to reduce diabetes risk in women with a gestational diabetes history in the American Diabetes Prevention Program trial, adoption of these health behaviours is low; qualitative studies confirm a need for tailored strategies that address barriers and provide social support. Further research is also needed on approaches to reduce vascular risk in women with a history of gestational diabetes and HDP. Otherwise, an early window of opportunity for chronic disease prevention in young, high-risk women will be missed.The Canadian journal of cardiology 01/2014; · 3.12 Impact Factor
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ABSTRACT: Hypertension remains the main risk factor for cardiovascular death. Environmental and biological factors are known to contribute to the condition, and circulating creatine kinase was reported to be the main predictor of blood pressure in the general population. This was proposed to be because of high resistance artery creatine kinase-BB rapidly regenerating ATP for vascular contractility. Therefore, we assessed whether creatine kinase isoenzyme mRNA levels in human resistance arteries are associated with blood pressure. We isolated resistance-sized arteries from omental fat donated by consecutive women undergoing uterine fibroid surgery. Blood pressure was measured in the sitting position. Vessels of 13 women were included, 6 normotensive and 7 hypertensive, mean age 42.9 years (SE, 1.6) and mean systolic/diastolic blood pressure, 144.8 (8.0)/86.5 (4.3) mm Hg. Arteriolar creatine kinase isoenzyme mRNA was assessed using quantitative real-time polymerase chain reaction. Normalized creatine kinase B mRNA copy numbers, ranging from 5.2 to 24.4 (mean, 15.0; SE, 1.9), showed a near-perfect correlation with diastolic blood pressure (correlation coefficient, 0.9; 95% confidence interval, 0.6-1.0) and were well correlated with systolic blood pressure, with a 90% relative increase in resistance artery creatine kinase B mRNA in hypertensives compared with normotensives, normalized copy numbers were, respectively, 19.3 (SE, 2.0) versus 10.1 (SE, 2.1), P=0.0045. To our knowledge, this is the first direct evidence suggesting that resistance artery creatine kinase mRNA expression levels concur with blood pressure levels, almost doubling with hypertension. These findings add to the evidence that creatine kinase might be involved in the vasculature's pressor responses.Hypertension 10/2013; · 6.87 Impact Factor