Review: Insulin and endothelin: an interplay contributing to hypertension development? (original) (raw)
Related papers
In vivo relationship between insulin and endothelin role of insulin-resistance
Journal of Human Hypertension, 1997
Since endothelin production is stimulated in vitro by insulin, we performed this study to evaluate in vivo the relationships between endothelin and insulin plasma levels during a glucose load. We studied 28 subjects; 17 with normal glucose tolerance (NGT) and 11 with impaired glucose tolerance (IGT). Ten of the subjects in this study were normotensive and 18 with mild to moderate hypertension. Age, sex and body mass index were comparable among the groups. After a 2-week period of washout they underwent an oral glucose tolerance test; blood was drawn at 0 (basal), 90 and 120 min after the load for determination of glucose, insulin, C-peptide of insulin and endothelin-1 and -2. Basal endothelin in all the subjects under study was correlated with basal insulin; moreover it was negatively related with the glucose:insulin ratio that has been considered as an insulin-sensitivity index and positively with the insulin:C-peptide ratio as hepatic insulin-resistance index. The relationship between basal endothelin and insulin values was also found in each glucose tolerance group. At 120 min after the glucose load, mean plasma values of endothelin were significantly higher (6.66 +/- 1.31 vs 4.17 +/- 0.61 pmol/L); moreover, the per cent increase of endothelin at 120 min was positively related to the per cent increase of insulin. Between the normotensive and hypertensive groups there were no significant differences in studied endothelin parameters. Our results appear to confirm that, even in vivo, insulin modulates circulating endothelin levels.
The role of endothelin-1 and nitric oxide in the pathogenesis of hypertension in diabetic patients
Collegium antropologicum, 2008
The pathogenesis of renal hypertension has not yet been fully clarified. As the potential role of endothelin-1 (ET-1) and nitric oxide (NO) has been postulated, their concentrations were determined in plasma and urine of diabetic patients. The study included 30 diabetic patients (both IDDM and NIDDM) with initial or advanced diabetic nephropathy (decreased endogenous creatinine clearance, proteinuria) and 20 healthy control subjects. The correlation with blood pressure and other renal function parameters was monitored and compared with the control group. Also, the effect of ACE inhibitors (ACEI) on ET-1 and NO patterns was monitored in correlation with arterial hypertension. In diabetic patients that did not receive ACEI therapy, the increase in plasma ET-1 was associated with both systolic and diastolic blood pressure elevation, whereas in those administered ACEI the increase in plasma ET-1 was associated with a systolic blood pressure decline. In addition, the increase in plasma N...
Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans
Diabetes, 1996
The purpose of the study was to evaluate fasting endothelin-1 levels in subjects with syndrome X, in subjects with insulinoma, and in normal subjects. The single and synergistic contributions of insulin and triglyceride levels to endothelin-1 release were studied in normal subjects. This was achieved by the evaluation of endothelin-1 levels in response to an insulin bolus combined with a euglycemic clamp (protocol A) and during intralipid (test 1) or saline (test 2) infusions lasting 360 min (protocol B). In protocol B, a euglycemic two-step hyperinsulinemic (25 and 125 mU-kg" 1^"1) clamp was started at 120 min. Subjects with syndrome X showed significantly higher endothelin-1 levels than normal subjects and subjects with insulinoma (7.22 ± 0.89 vs. 2.61 ± 0.38 and 2.49 ± 0.24 pg/ml, P < 0.01). After an insulin bolus, endothelin-1 levels peaked at 10 min (3.71 ± 0.96 pg/ml). The incremental area of endothelin-1 was significantly higher after insulin than after a saline bolus. In test 1, an acute increase in triglyceride levels significantly enhanced endothelin-1 levels, which were further increased by the synergistic contribution of high insulin and triglyceride levels. In test 2, endothelin-1 release was achieved at high insulin levels but remained significantly lower than in test 1. In conclusion, subjects with syndrome X showed higher endothelin-1 levels than normal subjects and subjects with insulinoma. These levels were reproduced in normal subjects by a simultaneous increase in insulin and triglyceride levels. Diabetes 45:316^321, 1996 C onsiderable attention has recently been placed on the potential role of endothelin-1 in vascular disease, since endothelin-1 is a potent vasoconstrictor peptide synthesized and secreted by endothelial cells (1-4). Increased endothelin-1 levels were described in a variety of pathological conditions, including essential hypertension (5-9), uremia (8), ischemic heart disease (9-11), and atherosclerosis (12). Endothelin-1 levels were also found at higher levels in patients with diabetes (13,14), although these data were not confirmed by others (15). The presence of low circulating endothelin-1 levels reported in some studies might be related to the predominant From the Istituto Scientiflco H.
A role for endothelin in the pathogenesis of hypertension: Fact or fiction?
Kidney International, 1998
A role for endothelin in the pathogenesis of hypertension: Fact or fiction? Endothelin-1 (ET-1) was discovered 10 years ago. Because it is one of the most potent vasoconstrictors in vivo, a pathophysiological role for the peptide as a mediator of hypertension has been postulated. Several clinical studies, however, have been unable to identify elevated ET levels in the plasma of hypertensive patients, suggesting that it does not play a prominent role in this disease. More recently, evidence has been presented that ETs act predominantly at the autocrine/paracrine level and that measurements of plasma levels can give only an indirect view of the activity of the system. In addition, transgenic technology has uncovered new actions of the peptide systems in recent years, which point to a key function of the system in prenatal development. Moreover, investigation of conditions associated with hypertensive end-organ damage, such as chronic renal failure, has led to a re-evaluation of the role of the ET system in hypertension. This article discusses this recent evidence and defines the exact role of the ET system in hypertension and hypertensive end-organ damage.
Role of Endothelin in the Pathogenesis of Hypertension
Mayo Clinic Proceedings, 2005
In 1985, investigators characterized a potent vasoconstrictor of endothelial origin called endothelin (ET). Subsequently, 3 peptides were recognized that had a comparable molecular structure but different receptors that mediate potent vasoconstrictive and mild vasodilative effects. The renal effects are characterized by natriuresis despite renal vasoconstriction. This effect, along with the stimulation of ET by high sodium intake, suggests that ET may be responsible for maintaining sodium balance when the reninangiotensin system is depressed. Endothelin is activated in desoxycorticosterone acetate salt hypertension models and salt-sensitive hypertension. However, ET involvement with spontaneous hypertension models and renovascular hypertension in rats appears minimal. In humans, the role of ET appears similar to that in experimental animals; in both, ET regulates salt metabolism. Saltsensitive patients exhibit a blunted renal ET-1 response during sodium load. The role of ET in humans has been investigated using nonspecific ET receptor blockers that inhibit the vasoconstrictive and vasodilative components of ET. However, the effects of ET blockade should be investigated with ET subtype A receptor blockers that mediate vasoconstriction alone. Effects of ET blockade also should be evaluated with respect to stimulation of oxidative stress and tissue damage, important mechanisms responsible for tissue fibrosis. This review offers the clinician a balanced view on the hypertensive mechanisms involved with activation of ET and associated clinical implications.
2021
The mechanisms that regulate blood pressure are numerous and complex; one mechanism that plays an important role in this scenario is represented by the balance between the vasoconstrictor effect of endothelin-1 and the vasodilator effect of nitric oxide. While there is agreement on the fact that increased endothelin-1 activity and decreased nitric oxide bioavailability are present in hypertensive adults, the situation is less clear in children and adolescents. Not all studies agree on the finding of an increase in plasma endothelin-1 levels in hypertensive children and adolescents; in addition, the picture is often confused by the concomitant presence of obesity, a condition that stimulates the production of endothelin-1. Furthermore, there is recent evidence that, in younger obese and hypertensive subjects, there is an overproduction of nitric oxide, rather than a reduction. This condition may change over time, causing endothelial dysfunction due to a reduced availability of nitric...