RESUMEN
Endothelins (ETs) are the peptides made up of 21 amino acids synthesized and released by variety of cells. Following studies revealed three isoforms of ETs-ET-1, ET-2 and ET-3. Endothelin ET-1 is known as the most potent endothelium-derived vasoconstrictor peptide identified so far. Endothelin ET-1 acts in a paracrine manner on the two types of receptors ET-A and ET-B. The former is responsible for the vascular smooth muscle constriction and the latter for vasodilation or vasoconstriction depending on the subtype of this receptor (ET-B1 or ET-B2 respectively). Endothelin receptor subtypes have been demonstrated and pharmacologically characterized in the coronary vascular bed. A good deal of experimental and clinical data has been accumulated to support an important role of endothelin-1 in ischemic heart disease. In experimental animals, exogenous ET-1 was found to cause coronary vasoconstriction and, at higher doses, ventricular fibrillation and death. The plasma levels of immunoreactive endothelin-1 were found to be increased in patients with coronary arteriosclerosis, acute myocardial infarction, and angina. The purpose of this study was to critically review the experimental and clinical data supporting the involvement of ET-1 in ischemic heart disease.
Asunto(s)
Enfermedad de la Arteria Coronaria/metabolismo , Vasos Coronarios/metabolismo , Endotelina-1/metabolismo , Receptores de Endotelina/metabolismo , Animales , Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Humanos , Isquemia Miocárdica/metabolismoRESUMEN
Endothelins (ETs) are peptides of 21 amino acids synthesized and released by variety of cells. Endothelin (now this peptide is called endothelin-1 (ET-1)) was isolated and identified in 1988 by Yanagisawa et al. Following studies revealed two other isoforms of endothelin': Endothelin-2 (ET-2) and endothelin-3 (ET-3). All of them bind to two types of receptors (A and B (ET-A r, ET-Br). ET-A r are responsible for concentration mediating. Two subtypes of ET-B r are known. ET-B1 r mediates vasorelaxation; ET-B2 vasoconstriction. ETs (especially ET-1) have variety of biological actions but the most important are vasoconstrictor and mitogenic action. Through these two mechanism ETs may participate in the pathogenesis and/or in the maintenance of hypertension in both experimental animal models and human essential hypertension. The intravenous infusion of synthetic ET induces a long-lasting elevation of blood pressure in experimental animals and in healthy humans. Number of studies have shown enhanced responses to ET in hypertensive subjects but decreased responses have also been reported. Similarly, plasma levels of ET-1 are either normal or elevated in experimental and human essential hypertension. Numerous investigators have suggested an interaction between ET and angiotensin-converting enzyme inhibitors through the renin-angiotensin system or through the accumulation of endogenous bradykinin. Also calcium antagonists of different classes prevent endothelin-induced contractions. Endothelin- converting enzyme inhibitor (phosphoramidon) and ET-A/B r antagonists (bosentan, BQ-123, FR139317) may have potential role as vasodilators in the treatment of hypertension.
Asunto(s)
Endotelinas/metabolismo , Hipertensión/metabolismo , Animales , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Endotelinas/efectos de los fármacos , Endotelinas/aislamiento & purificación , HumanosRESUMEN
OBJECTIVE: To determine whether the administration of acetylsalicylic acid (ASA, also known as Aspirin) differentiates patients with renovascular hypertension from those with essential hypertension, in order to provide a simple alternative to more expensive forms of diagnosis for this condition. DESIGN: Trial of ASA test in patients with previously diagnosed essential and renovascular hypertension. SETTING: Inpatient department of an academic health sciences centre in Poznan, Poland. PATIENTS: Forty patients with essential hypertension and 21 patients with renovascular hypertension. INTERVENTIONS: Patients were given an intravenous injection of ASA (10 mg/kg body weight), blood pressure was measured and blood was sampled and assayed for plasma renin activity (PRA) before and 30 minutes after the injection. RESULTS: ASA infusion in patients with renovascular hypertension resulted in a decrease in PRA from 15.2 (standard deviation [SD] 12.4) ng/mL per hour to 7.2 (SD 9.8) ng/mL per hour, whereas in patients with essential hypertension the initial PRA was significantly lower before ASA administration and did not change afterward. In patients with renovascular hypertension, the mean systolic, diastolic and arterial pressure decreased significantly (p < 0.001) after ASA infusion, but these did not change in patients with essential hypertension. Based on the criterion of 4 mm Hg as a detectable decrease in mean blood pressure, the sensitivity of the ASA test was 95.0% and the specificity 82.5%; its positive predictive value was 74% and its negative predictive value 97%. CONCLUSION: The precise measurement of blood pressure during the ASA test may provide a useful method of differentiating between patients with renovascular and essential hypertension.