Urocortin 2 - a protective effect in hypertension?

Urocortin 2, an endogenous selective ligand for the corticotropin-releasing hormone receptor type 2, has been suggested to exert cardioprotective effects. We analyzed the possible relationship between the level of Ucn2 and specific indicators of cardiovascular risk factors in patients with untreated hypertension and in healthy subjects. Sixty seven subjects were recruited: 38 with newly diagnosed treatment-naive hypertension (with no pharmacological treatment - HT group) and 29 healthy subjects without hypertension (nHT group). We evaluated ambulatory blood pressure monitoring, Ucn2 levels and metabolic indices. Multivariable regression analyses were performed to assess the effects of gender, age, and Ucn2 levels on metabolic indices or blood pressure (BP) level. Log of Ucn2 levels were higher in healthy subjects than in hypertensive patients (2.44±0.7 versus 2.09±0.66, p<.05) and correlated inversely with 24-hour diastolic blood pressure, and both night-time systolic and diastolic blood pressure regardless of age and gender (R2=0.06; R2=0.06; R2=0.052; respectively). Furthermore, Ucn2 levels inversely correlated with cholesterol and low-density cholesterol (LDL) concentrations in healthy subjects only. Ucn2 was independently related to total cholesterol (but not to LDL) regardless of age, gender and the presence of hypertension (R2=0.18). However, we did not find any relationship between urocortin 2, body mass index or waist-hip ratio as well as parameters of glucose metabolism. Our data indicates that higher levels of urocortin 2 are related to more favorable lipid profiles and lower blood pressure.

Urocortin 2 in patients with hypertension treated with angiotensin converting enzyme inhibitors or angiotensin receptor blockers.

Urocortin 2 (Ucn2) - corticotropin-releasing hormone receptor 2 signalling has favourable effects in the cardiovascular system, including vasodilation, lowering of blood pressure and systemic peripheral resistance, increase in cardiac output and cardiac contractility, as well as cardioprotection against ischemia-reperfusion injury. Vasodilation and lowering of blood pressure seem to be very interesting and important effects, but their mechanism and interaction with the antihypertensive drugs have not been evaluated. The aim of the present study was to assess the relationship between Ucn2 concentration and antihypertensive therapy in patients with primary hypertension. We examined a group of 65 patients with primary hypertension receiving at least 3 antihypertensive drugs. In all of them plasma level of Ucn2, anthropometric measurements, biochemical tests, ambulatory blood pressure monitoring (ABPM), and echocardiography were performed. There were no differences in Ucn2 level related to beta-blockers, calcium channel blockers or diuretics, but we observed that in patients treated with angiotensin converting enzyme inhibitors (ACEI) (n = 52) serum Ucn2 levels were significantly higher than in patients treated with angiotensin-receptor blockers (ARBs) (n = 13) (10.93 versus 5.56 ng/mL; P < 0.05). Moreover, we did not observe any differences in terms of blood pressure on ABPM, biochemical measurements, left ventricular mass index, or presence of diabetes. In addition, in a small subgroup receiving alpha-blockers we also found a lower level of Ucn2, with coexisting higher systolic blood pressure at night, higher left ventricle mass index (LVMI) and more frequent occurrences of diabetes compared to non-alpha-blockers. Our findings suggest that the hypotensive action of renin-angiotensin-aldosterone system blockade may be related to the urocortin system. Ucn2 may be an important element in the mosaic of blood pressure-lowering factors in patients treated for essential hypertension.

Arterial structure and function and its short- and long-term changes after bariatric surgery.

Subclinical arterial damage connected with endothelial dysfunction is a common denominator of cardiovascular complications in a variety of metabolic diseases, including obesity. The aims of the study was to assess functional vascular changes measured by flow-mediated dilatation (FMD) and nitroglycerin-mediated dilation (NMD) of brachial artery, and to measure vascular structural alterations estimated by carotid intima-media complex thickness (IMT) in short- (10 days) and medium-term (6 months) time after bariatric surgery in patients with extreme obesity. Anthropometric, blood pressure (BP), FMD, NMD, IMT measurements, and laboratory assessment were performed on patients who met the eligibility criteria for bariatric surgery (age 18 - 60 years old, BMI ≥ 40.0 kg/m2 or with BMI 35.0 - 39.9 kg/m2 and co-morbidities), at baseline and during follow-up. The study population consisted of 71 patients: mean SD aged 45.6 (± 10.9) years; BMI = 47.7 (± 6.1) kg/m2; 45% of them were men). A significant reduction of systolic BP, glucose, HDL cholesterol, leptin, insulin and HOMA-IR were observed 10 days post intervention. A significant increase of FMD values was observed in the entire group 6 months after surgery (median (IQR) 6.2 (2.9 - 10.3) versus 8.5 (6.1 - 16.6), P < 0.05). Changes of NMD were insignificant. Carotid IMT diminished significantly after 6 months (median (IQR) 0.6 (0.5 - 0.7) versus 0.6 (0.5 - 0.6) mm, P < 0.05). A subgroup analysis revealed that FMD parameters had improved significantly after 6 months, mainly in men, hypertensives, and in the Roux-en Y bypass (RYGB) subgroup. In conclusion, endothelial function and subclinical atherosclerosis improved after bariatric surgery in patients with extreme obesity. A lack of changes of the dilatation independent of endothelial function may indicate the persistence of residual changes in the vascular bed.

The role of urocortins in the cardiovascular system.

Urocortins (Ucn) 1, 2 and 3 are a group of endogenous peptide hormones belonging to the corticotropin-releasing hormone (CRH) family of peptides. The presence of urocortins has been detected in the central nervous system as well as in peripheral tissues. They play an important role in a stress response (with respect to its duration, intensity and restoration of homeostasis). They also act as regulatory factors of the cardiovascular, gastrointestinal, reproductive and immune systems. Urocortins act by binding to G-protein-coupled receptors (GPCR). The "central" effects of urocortins are mediated mainly by activation of CRH receptor 1 (CRH-R1), and the "peripheral" effects by activation of CRH-R2. Ucn2 and Ucn3 are selective CRH-R2 agonists and have much higher binding affinity to this receptor than CRH and Ucn1. Recent studies have shown that urocortins exert various biological effects in the cardiovascular system, such as vasodilation, positive inotropic and lusitropic effects, as well as cardioprotection against ischemia-reperfusion injury. They also suppress the renin-angiotensin system and may have an impact on the sympathetic nervous system. Urocortins and CRH-R2 may be a potential therapeutic target in coronary heart disease, congestive heart failure and hypertension. This review summarizes the data published to date on the role of urocortins in the cardiovascular system.