RESUMO
The effect of cromakalim, an opener of ATP-sensitive potassium (KATP) channel, on precontracted aortic rings from control and salt-loaded rats was studied in Sprague-Dawley rats. Salt-loading experiments involved the induction of hypertension by 6-week feeding of 80 g sodium chloride (NaCl) per kilogram (kg) diet while the control diet had 3 g NaCl per kg diet. Blood pressure and heart rate were determined by cannulation of a femoral artery under urethane/alpha-chloralose anaesthesia. Isolated aortic rings were mounted in tissue baths for isometric tension measurement. The sodium-potassium adenosine triphosphatase (Na-K ATPase) pump activity was measured by potassium (K+)-induced relaxation (with or without ouabain) following precontraction with 10(-7) M noradrenaline. The KATP channel was studied by measuring the relaxation response to cromakalim, precontracted with either 10(-7) M noradrenaline or 60 mM potassium chloride (KCl). The Na-K ATPase pump appeared to be inhibited during salt loading. ATPase inactivation was found to be ouabain sensitive but did not seem to affect subsequent K(+)-induced contraction. Cromakalim produced relaxation of noradrenaline-precontracted rings from the control rats; rings from salt-loaded rats showed significantly less relaxation than control (p < 0.05) under similar conditions. During K(+)-induced precontraction, cromakalim produced a weak biphasic response in the control rings--an initial relaxation and then a reversal. Cromakalim produced further contraction of K(+)-induced precontraction in the salt-loaded group. The results suggest that ATP-sensitive potassium channels and Na-K ATPase pumps on the vascular smooth muscle membrane may be deactivated in the development of hypertension during salt loading.
Assuntos
Cromakalim/farmacologia , Hipertensão/tratamento farmacológico , Músculo Liso Vascular/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Vasodilatadores/farmacologia , Adenosina Trifosfatases/fisiologia , Animais , Aorta/efeitos dos fármacos , Cromakalim/administração & dosagem , Hipertensão/induzido quimicamente , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Cloreto de Sódio na Dieta , Resultado do Tratamento , Vasodilatadores/administração & dosagemRESUMO
The effect of cromakalim, an opener of ATP-sensitive potassium (KATP) channel, on precontracted aortic rings from control and salt-loaded rats was studied in Sprague-Dawley rats. Salt-loading experiments involved the induction of hypertension by 6-week feeding of 80 g sodium chloride (NaCl) per kilogram (kg) diet while the control diet had 3 g NaCl per kg diet. Blood pressure and heart rate were determined by cannulation of a femoral artery under urethane/alpha-chloralose anaesthesia. Isolated aortic rings were mounted in tissue baths for isometric tension measurement. The sodium-potassium adenosine triphosphatase (Na-K ATPase) pump activity was measured by potassium (K+)-induced relaxation (with or without ouabain) following precontraction with 10(-7) M noradrenaline. The KATP channel was studied by measuring the relaxation response to cromakalim, precontracted with either 10(-7) M noradrenaline or 60 mM potassium chloride (KCl). The Na-K ATPase pump appeared to be inhibited during salt loading. ATPase inactivation was found to be ouabain sensitive but did not seem to affect subsequent K(+)-induced contraction. Cromakalim produced relaxation of noradrenaline-precontracted rings from the control rats; rings from salt-loaded rats showed significantly less relaxation than control (p < 0.05) under similar conditions. During K(+)-induced precontraction, cromakalim produced a weak biphasic response in the control rings--an initial relaxation and then a reversal. Cromakalim produced further contraction of K(+)-induced precontraction in the salt-loaded group. The results suggest that ATP-sensitive potassium channels and Na-K ATPase pumps on the vascular smooth muscle membrane may be deactivated in the development of hypertension during salt loading.
