Abstract 1141: Adaptation of Coronary Arteriolar Dilations to The Simultaneous Presence of Obesity and Hypertension: Role of Increased Nitric Oxide Sensitivity
Increased body weight and elevated blood pressure could lead to the development of hyperdynamic circulation requiring increased coronary blood flow. Thus, we aimed to characterize the effects of simultaneous presence of obesity and hypertension on the dilator function of human coronary arterioles. Agonist-induced dilations were assessed in pressurized coronary arterioles isolated from the right atrial appendages of patients (N=38), that underwent cardiac surgery. There were no significant differences in bradykinin (BK)-induced and the nitric oxide (NO)-donor, sodium-nitroprusside (SNP)-evoked dilations of coronary arterioles between normotensive and hypertensive lean patients. In contrast, in the obese, normotensive patients BK- and SNP-induced dilations were reduced (BK, 10−7M, lean:90±4%, obese:64±7%; SNP, 10−6M, lean:89±7%, obese:76±5%), whereas in the obese, hypertensive patients BK- and SNP-induced dilations were significantly enhanced, when compared to lean subjects (BK, 10−7M, lean:71±7%, obese:85±3%; SNP, 10−6M, lean:60±6%, obese:83±2%). Correspondingly, in hypertensive individuals, but not in those of normotensives, a positive correlation was found between body mass index (BMI) and bradykinin-induced (P=0.03, r=0.46), and also SNP-evoked (P<0.03, r=0.44) coronary dilations. To correlate coronary responses to those of peripheral vessels, in an additional 55 hypertensive patients flow-mediated (FMD) and nitroglycerin (NTG)-induced dilations were assessed by high-resolution ultrasound. In obese, hypertensive individuals both FMD and NTG-induced dilations were significantly greater (FMD:6.2±0.7%, NTG:17.2±0.9%), than in lean hypertensive patients (FMD:3.7±0.6%, NTG:13.6±1.1%). Correspondingly, both FMD and NTG-induced dilations were positively correlated with BMI, (P=0.02, r=0.31, P=0.03, r=0.29, respectively). These findings are the first to show that in humans obesity may lead to activation of an adaptive vascular mechanisms in hypertension, such as an increased sensitivity to NO, enhancing the dilator function of coronary and peripheral arterial vessels.