Kinins mediate the inhibition of atrial natriuretic peptide diuretic effect induced by pepsanurin

Pepsanurin is a peptidic fraction resulting from pepsin digestion of plasma globulins, that inhibits ANP renal excretory actions. We studied whether kinin-like peptides mediate the anti-ANP effect by testing if pepsanurin: 1) was blocked by the kinin B12 receptor antagonist HOE-140, 2) was produced from kininogen, and 3) was mimicked by bradykinin. Anti-ANP activity was assessed in anesthetized female rats by comparing the excretory response to two ANP boluses (0.5 mug iv) given before and after ip injection of test samples. Pepsanurin from human or rat plasma (1-5 mL/Kg), and bradykinin (5-20 mug/Kg), dose-relatedly inhibited ANP-induced water, sodium, potassium and cyclic GMP urinary excretion, without affecting arterial blood pressure. The same effect was exerted by pepsin hydrolysates of purified kininogen, whereas hydrolysates of kininogen-free plasma had no effect. HOE-140 (5 mug, iv) did not alter baseline, or ANP-induced excretion, but blocked the anti-ANP effects of pepsanurin. Histamine (15 mug/Kg) plus seroalbumin hydrolysates did not affect ANP response, despite inducing larger peritoneal fluid accumulation as compared with pepsanurin or bradykinin. We concluded that kinins cleaved from kininogen mediate the anti-ANP effects of pepsanurin by activation of kinin B2 receptors, independently of changes in systemic arterial pressure or peritoneal fluid sequestration.

Characterization of a new Kinin potentiating peptide obtained from human plasma proteins

Partially purified kinin potentiating peptide (KPP) obtained from kininogen-depleted human plasma inhibited lung angiotensin converting enzyme in vitro and potentiated guinea-pig ileum contractions induced by bradykinin (BK), Lys-BK, Met-Lys-BK, Ile-Ser-BK, and Lys-Lys-BK. Contractions evoked by angiotensin II, histamine, acetylcholine, and barium cloride were not potentiated. KPP also potentiated kinin-induced contractions of rat uterus and of guinea-pig ileum pre-incubated with 1,10-phenbabthroline. It in suggested that KPP potentiation is due, at least in part, to a direct effect on kinin receptor(s)

Modificaçöes seqüencias dos sistemas renina-angiotensina-aldosterona e calicreína-cinina na gestaçäo normal / Sequential modification of the renin-angiotensin-aldosterone and Kallikrein-Kinin systems in normal pregnancy

Avaliou-se o comportamento dos componentes do sistema renina-angiotensina-aldosterona (SRAA) e do sistema calicreína-cinina (SCC) e as conseqüências das mudanças posturais sobre a pressäo arterial (PA), diurese, natriurese e caliurese em diferentes fases da gravidez normal. Foram estudadas 15 gestantes no 1§, 2§, e 3§ trimestres da gestaçäo e 5 meses após o parto, momento em que se procedeu às determinaçöes da fase controle. Em cada fase de análise as pacientes adotavam, durante 90 minutos, o decúbito dorsal, o decúbito lateral esquerdo e a ortostasia. Verificou-se importante ativaçäo dos componentes do SRAA durante o ciclo gravídico e as mudanças posturais modificaram significativamente os valores da atividade plasmática de seus componentes. No 2§ e 3§ trimestres o decúbito lateral esquerdo, comparado com as outras posiçöes, reduziu a atividade plasmática de renina e a aldosteronemia e ocasionou, por outro lado, o aumento da diurese, natriurese e caliurese. A análise do SCC mostrou que determinados componentes desse sistema variam substancialmente durante a gravidez, observando-se reduçäo progressiva nos níveis de cininogênio e de pré-calicreína e elevaçäo da calicreína circulante. As mudanças posturais näo interferiram nos valores dos componentes plasmáticos desse sistema. Os níveis do fator potenciador de cininas näo se alteraram na gestaçäo. A excreçäo urinária de calicreína elevou-se até o 2§ trimestre e as mudanças posturais modificaram a excreçäo urinária da enzima. A PA e os níveis séricos de sódio e potássio mantiveram-se normais, sem diferenças significativas, quando foram consideradas as mudanças posturais e os periódos de gestaçäo. Conclui-se que a hiperatividade do SRAA, e o consumo significante de cininogênio e as modificaçöes na diurese, natriurese e caliurese se harmonizam de modo a manter normal a PA e o metabolismo hidrossalino