Olmesartan-associated Enteropathy with Acute Kidney Injury / 대한소화기학회지

Olmesartan, a recently introduced angiotensin II receptor blocker for hypertension, has been reported to cause drug-induced small bowel enteropathy. The diagnosis of olmesartan-associated enteropathy (OAE) needs clinical suspicion and the exclusion of coeliac disease, as it mimics coeliac sprue. Once diagnosed, it can be completely cured with the discontinuation of olmesartan. However, due to the extremely low incidence of OAE in Korea, clinical suspicion and diagnosis may be a challenge. The authors report the first case of OAE presenting with chronic diarrhea and acute kidney injury in Korea.

Mechanism of Leptin-Induced Potentiation of Catecholamine Secretion Evoked by Cholinergic Stimulation in the Rat Adrenal Medulla

The aim of the present study was to examine the effect of leptin on CA release from the isolated perfused model of the rat adrenal gland, and to establish its mechanism of action. Leptin (1~100 ng/ml), when perfused into an adrenal vein of the rat adrenal gland for 60 min, enhanced a dose-dependently the secretory responses of CA evoked by ACh (5.32x10 (-3)M), DMPP (10 (-4)M) and McN-A-343 (10 (-4)M), although it alone has weak effect on CA secretion. However, it did not affect the CA secretion evoked by excess K+ (5.6x10 (-2)M). Leptin alone produced a weak secretory response of the CA. Moreover, leptin (10 ng/ml) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type Ca2+ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic Ca2+ ATPase. However, in the presence of U0126 (1micrometer), an inhibitor of mitogen-activated protein kinase (MAPK), leptin no longer enhanced the CA secretion evoked by ACh and DMPP. Furthermore, in the presence of anti-leptin (10 ng/ml), an antagonist of Ob receptor, leptin (10 ng/ml) also no longer potentiated the CA secretory responses evoked by DMPP and Bay-K-8644. Collectively, these experimental results suggest that leptin enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors), but does not that by membrane depolarization. It seems that this enhanced effect of leptin may be mediated by activation of U0126-sensitive MAPK through the leptin receptors, which is probably relevant to the activation of the dihydropyridine L-type Ca2+ channels located on the rat adrenomedullary chromaffin cells.

Influence of Bradykinin on Catecholamine Release from the Rat Adrenal Medulla

The present study was undertaken to investigate the effect of bradykinin on secretion of catecholamines (CA) evoked by stimulation of cholinergic receptors and membrane depolarization from the isolated perfused model of the rat adrenal glands, and to elucidate its mechanism of action. Bradykinin (3 X 10 (-8) M) alone produced a weak secretory response of the CA. however, the perfusion with bradykinin (3 X 10 (-8) M) into an adrenal vein of the rat adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by ACh (5.32 X 10 (-3) M), excess K+ (5.6 X 10 (-2) M, a membrane depolarizer), DMPP (10 (-4) M, a selective neuronal nicotinic agonist) and McN-A-343 (10 (-4) M, a selective M1-muscarinic agonist). Moreover, bradykinin (3 X 10 (-8) M) in to an adrenal vein for 90 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type Ca2+ channels. However, in the presence of (N-Methyl-D-Phe7) -bradykinin trifluoroacetate salt (3 X 10 (-8) M), an antagonist of BK2-bradykinin receptor, bradykinin no longer enhanced the CA secretion evoked by Ach and high potassium whereas the pretreatment with Lys- (des-Arg9, Leu8) -bradykinin trifluoroacetate salt (3 X 10 (-8) M), an antagonist of BK1-bradykinin receptor did fail to affect them. Furthermore, the perfusion with bradykinin (3 X 10 (-6) M) into an adrenal vein of the rabbit adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by excess K+ (5.6 X 10 (-2) M). Collectively, these experimental results suggest that bradykinin enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization through the activation of B2-bradykinin receptors, not through B1-bradykinin receptors. This facilitatory effect of bradykinin seems to be associated to the increased Ca2+ influx through the activation of the dihydropyridine L-type Ca2+ channels.