peptide-yy and Hypertrophy--Left-Ventricular

Hypertension is a major health problem and is usually associated with common conditions such as obesity, which contribute to clinical cardiac dysfunction. The role of energy homeostasis hormones such as ghrelin and PYY 3-36 in cardiovascular function remains incompletely understood. Therefore, the aim of our study was to explore the potential differences in concentrations of ghrelin forms and PYY 3-36 circulating in obese patients with grade 1 and grade 2 hypertension, with higher and lower BMI and without and with insulin resistance as well as to determine whether these hormones may be associated with left ventricular hypertrophy.. A total of 142 adult subjects were studied in three subgroups: lean (BMI < 25 kg/m(2)) normotensive subjects and obese subjects (BMI 30.0-34.9 kg/m(2)), and obese subjects (BMI 35.0-39.9 kg/m(2)) under hypertensive treatment for at least 9 years. Fasting blood glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), lipid profile, urinic acid, acylated ghrelin (A-Ghr), total ghrelin (T-Ghr), and PYY 3-36 were measured. Insulin resistance was determined by the homeostasis model assessment of insulin resistance (HOMA-IR). We also echocardiographically assessed left ventricular mass (LVM) index (LVMI = LVM/height(2.7)). We evaluated the association between plasma T-Ghr, A-Ghr, PYY 3-36 levels with LVMI and other measured factors using univariate and multivariate analysis.. There were significant differences between BMI, waist circumference (WC), LVMI, hs-CRP and A-Ghr/nonacylated ghrelin (NA-Ghr) ratio (in the two obese subgroups. There was no significant difference between T-Ghr, A-Ghr and PYY 3-36 levels between obese subgroups. T-Ghr and PYY 3-36 were significantly lower in obese patients than in the control group, whereas A-Ghr levels did not differ between obese and controls. A-Ghr/NA-Ghr ratio was significantly higher in patients with second-degree hypertension and BMI 35.0-39.9 kg/m(2) than in patients with first-degree hypertension and BMI 30.0-34.9 kg/m(2). There were negative associations between T-Ghr, NA-Ghr or PYY 3-36 and LVMI (r = -0.49, p = 0.0001; r = -0.47, p = 0.0001; or r = -0.18, p = 0.029, respectively) and positive association between A-Ghr/NA-Ghr ratio and LVMI (r = 0.3, p = 0.0003). T-Ghr and NA-Ghr, were associated negatively with fasting insulin (r = -0.31, p = 0.0025; and r = -0.36, p = 0.001, repectively), while A-Ghr/NA-Ghr ratio was positively associated with BMI and fasting insulin (r = 0.23, p = 0.041; r = 0.3, p = 0.0045, respectively). T-Ghr, A-Ghr, and NAGhr were also inversely related to HOMA-IR indices in obese patients (r = -0.43, p = 0.001; r = -0.32, p = 0.0359; r = -0.35, p = 0.001, respectively). In insulin-resistant obese subjects T-Ghr and NA-Ghr correlated negatively with HOMA-IR (r = -0.34, p = 0.0015; r = -0.28, p = 0.0116, respectively). LVMI was associated negatively with T-Ghr, NA-Ghr and PYY 3-36 (r = -0.49, p = 0.0001; r = -0.47, p = 0.0001; r = -0.18, p = 0.029, respectively). In addition, LVMI was positively associated with A-Ghr/NA-Ghr ratio (r = 0.30, p = 0.0003).. Plasma ghrelin forms and PYY 3-36 levels are associated with LVMI. These associations indicate a possible interaction between gut peptides and the cardiovascular system in hypertension and obesity.

Topics: Acylation; Adult; Body Mass Index; C-Reactive Protein; Female; Ghrelin; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin; Insulin Resistance; Male; Middle Aged; Multivariate Analysis; Obesity; Peptide YY; Reference Values; Waist Circumference

Severity of left ventricular hypertrophy (LVH) correlates with elevated plasma levels of neuropeptide Y (NPY) in hypertension. NPY elicits positive and negative contractile effects in cardiomyocytes through Y(1) and Y(2) receptors, respectively. This study tested the hypothesis that NPY receptor-mediated contraction is altered during progression of LVH. Ventricular cardiomyocytes were isolated from spontaneously hypertensive rats (SHRs) pre-LVH (12 weeks), during development (16 weeks), and at established LVH (20 weeks) and age-matched normotensive Wistar Kyoto (WKY) rats. Electrically stimulated (60 V, 0.5 Hz) cell shortening was measured using edge detection and receptor expression determined at mRNA and protein level. The NPY and Y(1) receptor-selective agonist, Leu(31)Pro(34)NPY, stimulated increases in contractile amplitude, which were abolished by the Y(1) receptor-selective antagonist, BIBP3226 [R-N(2)-(diphenyl-acetyl)-N-(4-hydroxyphenyl)methyl-argininamide)], confirming Y(1) receptor involvement. Potencies of both agonists were enhanced in SHR cardiomyocytes at 20 weeks (2300- and 380-fold versus controls). Maximal responses were not attenuated. BIBP3226 unmasked a negative contraction effect of NPY, elicited over the concentration range (10(-12) to 3 x 10(-9) M) in which NPY and PYY(3-36) attenuated the positive contraction effects of isoproterenol, the potencies of which were increased in cardiomyocytes from SHRs at 20 weeks (175- and 145-fold versus controls); maximal responses were not altered. Expression of NPY-Y(1) and NPY-Y(2) receptor mRNAs was decreased (55 and 69%) in left ventricular cardiomyocytes from 20-week-old SHRs versus age-matched WKY rats; parallel decreases (32 and 80%) were observed at protein level. Enhancement of NPY potency, producing (opposing) contractile effects on cardiomyocytes together with unchanged maximal response despite reduced receptor number, enables NPY to contribute to regulating cardiac performance during compensatory LVH.

Topics: Animals; Arginine; Calcium; Cardiotonic Agents; Cell Differentiation; Cell Separation; Cell Size; Electric Stimulation; Hypertrophy, Left Ventricular; Isoproterenol; Male; Membrane Proteins; Myocardial Contraction; Myocytes, Cardiac; Peptide Fragments; Peptide YY; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Neuropeptide Y; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger