Angiotensin II type 1 receptor A1166C gene polymorphism and essential hypertension in Calabar and Uyo cities, Nigeria.

OBJECTIVES: The angiotensin II protein is a vasoconstrictor that exerts most of its influence through the angiotensin II type 1 receptor (AT1R). Inconsistent association between the A1166C polymorphism of the AT1R gene and hypertension has been reported among various populations but not among the peoples of Calabar and Uyo. This study was designed to determine the frequency of the A1166C polymorphism of the AT1R gene and its association with hypertension in a sample population of Calabar and Uyo. MATERIALS AND METHODS: A population-based case control design consisting of total of 1224 participants, 612 each of patients and controls were randomly recruited from hypertension clinics and the general population. Genotyping of the A1166C allele of the AT1R gene to identify variants was performed using polymerase chain reaction and restriction enzyme digestion. Multiple regressions were applied to test whether the A1166 genotypes were predictors of hypertension. RESULTS: 99% of the study population had the wild type AA genotype, and 1% was AC heterozygous carriers of the A1166C polymorphism. CONCLUSION: The A1166C polymorphism was not a predictor of hypertension in the sample population of Calabar and Uyo.

Caracterización de un modelo de diabetes tipo 2 en ratas y evaluación del papel de la angiotensina II y las especies reactivas de oxígeno en la resistencia neuronal a la insulina / Characterization of a type 2 diabetes model in rats and evaluation of the role of angiotensin II and reactive oxygen species in neuronal insulin resistance

La regulación ejercida por la insulina central en individuos diabéticos ha sido muy poco estudiada. La angiotensina II promueve el estrés oxidativo y la resistencia a la insulina. Dada la co-localización del receptor AT1 de la angiotensina II y el RI a nivel hipotalámico, en este trabajo, decidimos evaluar el efecto de la angiotensina II sobre las acciones centrales de la insulina en condiciones diabéticas, a través de un modelo animal de DM2 en ratas Sprague-Dawley, así como el posible efecto protector del tratamiento crónico con Valsartán. El modelo fue caracterizado y validado a través de la medición de diversos parámetros metabólicos, usando técnicas enzimáticas e inmunoenzimáticas. Los efectos de la angiotensina II sobre la señalización y acciones biológicas de la insulina a nivel hipotalámico fueron evaluadas in vivo e in vitro, mediante western blot, así como los cambios en los niveles de glicemia en las ratas tratadas ICV con ANG II y/o insulina. Fue evaluado además, el estado oxidativo a nivel hipotalámico, mediante la determinación de enzimas antioxidantes, así como el estado inflamatorio sistémico, mediante la determinación fluorométrica de citoquinas plasmáticas. El modelo experimental desarrollado mimetizó las características fenotípicas de la DM2. El valsartán previno parcialmente la resistencia a la insulina. En condiciones normales, se demostró que la angiotensina es capaz de inhibir la señalización de la insulina a nivel hipotalámico por un mecanismo dependiente de ERO. En condiciones diabéticas, hay una disminución basal de la activación de las proteínas de señalización de la insulina, la cual fue prevenida por el tratamiento con valsartán. El efecto hipoglicemiante inducido por la insulina central fue significativamente reducido en condiciones diabéticas. El tratamiento ICV con angiotensina II antagonizó los efectos hipoglicemiantes de la insulina central y este efecto fue potenciado en condiciones diabéticas. El valsartán bloquea la acción inducida por la ANG II ICV en todos los grupos. Los resultados demuestran que existe un estado de resistencia a la insulina en nuestro modelo de DM2, evidente tanto a nivel molecular como fisiológico, el cual es potenciado por la angiotensina y prevenido parcialmente por el tratamiento crónico con valsartán.

1-Sarcosine - Angiotensin II tachyphylaxis in helical strips and everted rings of rabbit aorta

The development of tachyphylaxis to [1-sarcosine]-angiotensin II was studied in helical strips and everted rings of rabbit aorta. Strips, but not everted rings, developed marked (>50%) tachyphylaxis to the peptide, when challenged repeatedly at 1-h intervals. Measurements of the membrane potential showed no difference between the two preparations, but strips were more sensitive to KC1 than everted rings. These results suggest that the strips are more depolarized than the everted rings due to lesions caused by the spiral cutting. This partial depolarization may underlie the tachyphylactic phenomenon

Effects of intracerebroventricular infusion of angiotensin II and related peptides on water and sodium ingestion and excretion

The objetive of the present study was to investigate the effects of an angiotensin II (AII) analogue, Des-Asp1-AII and of two competitive blockers, [Leu8]-AII and [octanoyl-Leu8]-AII, infused intracerebroventriculary on the ingestion of water and of a 3% NaCl solution, as well as on diuresis and natriuresis in normal rats and in adrenalectomized and deoxycorticosterone (DOCA)-treated rats. Both AII and Des-Asp1-AII increased water and 3% NaCl intake and increased urine and Na+ excretion, the effect of AII being more intense. Except for 3% NaCl, the responses of all other parameters were totally or partially reduced by previous treatment with [Leu8]-AII or [octanoyl-Leu8]-AII. Subcytaneous DOCA injection caused water ingestion. Previous treatment with DOCA increased the response to AII for the ingestion of 3% NaCl and inhibited sodium excretion. The results obtained for adrenalectomized rats treated with DOCA, AII and analogous agonists did not differ from those observed in normal rats. These data suggest a possible synergism between the cerebral and renal renin-angiotensin systems in the regulation of the physiological parameters studied

Conformationally restricted analogs of angiotensin II: titration and biological activity

1. Six conformationally restricted analogues of angiotension II containing one disulfide bridge were synthesized by the solid-phase method. 2. These cyclic analogues were tirated electrometically and spectrophotometrically and their biological activites were assayed on the isolated guinea pig ileum and rat blood pressure. 3. The conformation restrictions led to significant differnces in the pKa values of a the titratable groups in al six analogs. 4. The comparison of tiration data between the cyclic and linear analogs of angiotension II indicates that in the pH range 4 to 9, angiotension II has a preferential folded conformation. An expanded conformation is assumed to occur at pH below 4 and above 9. 5. The biological activites of all cyclic analogs were less than 0.2% of the activity of angiotension II in toth bioassays