Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bile flow may be considerably increased in human cirrhosis. The mechanism of this increase has not been established. Two mechanisms have been proposed: a) increased canalicular filtration because of sinusoidal hypertension, or b) secretion by proliferated bile ductules. To distinguish between these two possibilities, we examined the determinants of bile secretion in rats with secondary biliary cirrhosis after bile duct obstruction. Sham-operated animals served as controls. Four weeks after bile duct ligation, all animals had cirrhosis. Bile flow was significantly higher and bile salt secretion significantly lower in cirrhotic animals than in controls. Biliary bicarbonate concentration was significantly higher in cirrhotic animals than in controls. Bile-to-plasma concentration ratio of erythritol was significantly lower in cirrhotic animals than in controls, suggesting a dilution of erythritol by a secretion distal to bile canaliculi. Bile-to-plasma ratio of sucrose was not significantly different in cirrhotics and controls, suggesting that paracellular permeability was not modified. Secretin, at the dose of 3 clinical units/100 g, induced an increase of approximately 75 percent in bile flow, and 70 percent in biliary bicarbonate concentration in cirrhotics. In conclusion, bile flow was increased in biliary cirrhosis in rats. The dilution of erythritol, the increase in biliary bicarbonate concentration and the increased response to secretin strongly suggest that increased choleresis was due, at least in part, to secretion by bile ductules or ducts. These results confirm that secondary biliary cirrhosis is a good experimental model for the study of alterations of bile secretion in cirrhosis.
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PMID:[An increase of choleresis in secondary biliary cirrhosis in rats is caused by bile duct secretion]. 235 Dec 43

We have assessed the presence of VIP/PHI/secretin receptors in heart by: (1) testing the ability of the corresponding peptides to activate adenylate cyclase in cardiac membranes from rat, dog, Cynomolgus monkey and man, and (2) examining the ability of the same peptides to exert inotropic and chronotropic effects on heart preparations from rat and Cynomolgus monkey in vitro. Based on their affinity for natural peptides and synthetic analogs, two types of VIP/PHI/secretin receptors were characterized: the relatively nonspecific "secretin/VIP receptor" of rat heart (that is "secretin-preferring" only in that secretin was more efficient than VIP in stimulating adenylate cyclase), and the "VIP/PHI-preferring" receptor of man, monkey and dog heart. Four physiopathological situations affecting secretin/VIP receptors in rat heart were explored: In male rats from the Okamoto strain and the Lyon strain, two strains presenting spontaneous hypertension, heart membranes exhibited a markedly decreased response of adenylate cyclase to secretin/VIP, with lesser alterations in the responses to isoproterenol and glucagon. This impairment developed in parallel with the occurrence of hypertension and was reproduced in normotensive rats submitted to chronic isoproterenol treatment (but not in Goldblatt hypertensive rats). These findings are consistent with a hyperactivity of norepinephrine pathways in spontaneously hypertensive rats, leading to a reduced number of cardiac post-junctional secretin/VIP receptors bound to adenylate cyclase. Heart membranes from genetically obese (fa/fa) Zucker rats also exhibited severely decreased responses to secretin/VIP with lesser alterations in the responses to glucagon and isoproterenol. These anomalies were specific for the heart, and developed in concomitance with obesity. The first anomaly could not be corrected by severe food restriction. Secretin stimulation of heart adenylate cyclase was also selectively altered in streptozotocin-diabetic rats. Thus, two types of diabetic cardiomyopathy were characterized by a severe local alteration of secretin/VIP receptors coupled to adenylate cyclase. Hypothyroidism, provoked in rat by thyroidectomy or propylthiouracil treatment, again induced a marked decrease in secretin-stimulated cardiac adenylate cyclase activity. In rat papillary muscle electrically stimulated in vitro, secretin exerted a positive inotropic effect. This effect was reduced in obese (fa/fa) Zucker rats. In rat right atrium, secretin also exerted a positive chronotropic effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Heart receptors for VIP, PHI and secretin are able to activate adenylate cyclase and to mediate inotropic and chronotropic effects. Species variations and physiopathology. 608 34