Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 Urotensin-II (U-II) is among the most potent mammalian vasoconstrictors identified and may play a role in the aetiology of essential hypertension. Currently, only one mouse U-II receptor (UT) gene has been cloned. It is postulated that this protein is solely responsible for mediating U-II-induced vasoconstriction. 2 This hypothesis has been investigated in the present study, which assessed basal haemodynamics and vascular reactivity to hU-II in wild-type (UT((+/+))) and UT receptor knockout (UT((-/-))) mice. 3 Basal left ventricular end-diastolic and end-systolic volumes/pressures, stroke volumes, mean arterial blood pressures, heart rates, cardiac outputs and ejection fractions in UT((+/+)) mice and in UT((-/-)) mice were similar. 4 Relative to UT((+/+)) mouse isolated thoracic aorta, where hU-II was a potent spasmogen (pEC(50)=8.26+/-0.08) that evoked relatively little vasoconstriction (17+/-2% 60 mM KCl), vessels isolated from UT((-/-)) mice did not respond to hU-II. However, in contrast, the superior mesenteric artery isolated from both the genotypes did not contract in the presence of hU-II. Reactivity to unrelated vasoconstrictors (phenylephrine, endothelin-1, KCl) and endothelium-dependent/independent vasodilator agents (carbachol, sodium nitroprusside) was similar in the aorta and superior mesenteric arteries isolated from both the genotypes. 5 The present study is the first to directly link hU-II-induced vasoconstriction with the UT receptor. Deletion of the UT receptor gene results in loss of hU-II contractile action with no 'nonspecific' alterations in vascular reactivity. However, as might be predicted based on the limited contractile efficacy recorded in vitro, the contribution that hU-II and its receptor make to basal systemic haemodynamics appears to be negligible in this species.
 ...
PMID:Deletion of the UT receptor gene results in the selective loss of urotensin-II contractile activity in aortae isolated from UT receptor knockout mice. 1277 Sep 52

Urotensin-II, a potent mammalian vasoconstrictor, may play a role in the etiology of essential hypertension. However, a species suitable for assessing such a role, one where a "classical" systemic hypertensive response (increase in mean blood pressure and systemic vascular resistance) is observed following bolus i.v. urotensin-II administration, has yet to be identified. The present study demonstrates that the cat may represent such a species since urotensin-II potently (pEC(50)s 9.68+/-0.24-8.73+/-0.08) and efficaciously (E(max) 73+/-15%-205+/-21% KCl) constricts all feline isolated arteries studied (aortae, renal, femoral, carotid, and mesenteric conduit/resistance). Accordingly, exogenous urotensin-II (1 nmol/kg, i.v.) effectively doubles both mean blood pressure (from 99+/-14 to 183+/-15 mmHg) and systemic vascular resistance (from 0.36+/-0.12 to 0.86+/-0.20 mmHg/ml/min) in the anaesthetized cat (without altering heart rate or stroke volume). Thus, in view of these profound contractile effects, the cat could be suitable for determining the effects of urotensin-II receptor antagonism on cardiovascular homeostasis in both normal and diseased states.
 ...
PMID:Urotensin-II: a novel systemic hypertensive factor in the cat. 1498 40

Urotensin-II (U-II) potently contracts some large isolated blood vessels and cardiac tissue. However, the maximum effects on human blood vessels and heart are relatively small. U-II dilates human resistance arteries. It markedly decreased myocardial function and increased vascular resistance in cynomolgus monkeys, but the major effects of U-II have not been observed in healthy humans. A major role for U-II in human cardiovascular disease has not been clearly established despite studies in patients with coronary artery disease, heart failure, essential hypertension and diabetes. Peptide and non-peptide agonists and antagonists of the U-II receptor are being developed and will be useful in the characterisation of the effects of U-II, and may have some therapeutic potential.
 ...
PMID:Urotensin-II and the cardiovascular system--the importance of developing modulators. 1515 23

Salusin-alpha is a new bioactive peptide with mild hypotensive and bradycardic effects. Our recent study showed that salusin-alpha suppresses foam cell formation in human monocyte-derived macrophages by down-regulating acyl-CoA:cholesterol acyltransferase-1, contributing to its anti-atherosclerotic effect. To clarify the clinical implications of salusin-alpha in hypertension and its complications, we examined the relationship between serum salusin-alpha levels and carotid atherosclerosis in hypertensive patients. The intima-media thickness (IMT) and plaque score in the carotid artery, blood pressure, serum levels of salusin-alpha, and atherosclerotic parameters were determined in 70 patients with essential hypertension and in 20 normotensive controls. There were no significant differences in age, gender, body mass index, fasting plasma glucose level, or serum levels of high-sensitive C-reactive protein, high- or low-density lipoprotein (LDL) cholesterol, small dense LDL, triglycerides, lipoprotein(a), or insulin between the two groups. Serum salusin-alpha levels were significantly lower in hypertensive patients than in normotensive controls. The plasma urotensin-II level, maximal IMT, plaque score, systolic and diastolic blood pressure, and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly greater in hypertensive patients than in normotensive controls. In all subjects, maximal IMT was significantly correlated with age, systolic blood pressure, LDL cholesterol, urotensin-II, salusin-alpha, and HOMA-IR. Forward stepwise multiple linear regression analysis revealed that salusin-alpha levels had a significantly independent and negative association with maximal IMT. Serum salusin-alpha levels were significantly lower in accordance with the severity of plaque score. Our results suggest that the decrease in serum salusin-alpha, an anti-atherogenic peptide, may be associated with carotid atherosclerosis in hypertensive patients.
 ...
PMID:Serum salusin-alpha levels are decreased and correlated negatively with carotid atherosclerosis in essential hypertensive patients. 1849 65