guanylin and Hypertension

More than 20% of adults in industrialized countries display arterial pressure outside the normal physiological range. For most individuals, the molecular basis of hypertension remains unknown. In some hypertensive persons, a postprandial natriuretic response, normally elicited by a salty meal, is diminished and contributes to body sodium accumulation and plasma volume expansion. An important physiological mechanism ensuring the increased salt excretion following ingestion of salt is based on a luminocrine and endocrine secretion of novel small intestinal peptides--guanylins. Membrane guanylate cyclase receptors mediate effects of these peptides that provide a novel link between the intestine and kidney by means of circulating molecular guanylin forms. It can be expected that the emergence of the novel guanylin signaling pathways will energize search for molecular defects causing hypertension.

Topics: Animals; Gastrointestinal Hormones; Humans; Hypertension; Intestines; Kidney; Natriuresis; Natriuretic Peptides; Peptides; Postprandial Period

Guanylin (GN), uroguanylin (UGN) and the GC-C receptor have been associated with two endocrine axes: the salt and water homeostasis regulating enterorenal axis and the recently described appetite-regulating UGN/GC-C extraintestinal axis. The present work assessed the mRNA expression levels of GN peptides system (GPS) in a model of diet-induced obesity. Male C57BL/6J mice were submitted to either a high-fat high-simple carbohydrate diet (obese) or a normal diet (control). The renal and intestinal GN, UGN and GC-C receptor mRNA expression were evaluated by reverse transcriptase quantitative polymerase chain reaction in both groups, during normo-saline (NS) and high-saline (HS) diet. The diet-induced obesity was accompanied by glucose intolerance and insulin resistance as well as by a significant increase in blood pressure. During NS diet, obese mice presented reduced mRNA expression of GN in ileum and colon, UGN in duodenum, ileum and colon and GC-C in duodenum, jejunum, ileum and colon. This was accompanied by increased UGN mRNA expression in renal cortex. During HS diet, obese mice presented reduced mRNA expression of GN in jejunum as well as reduced mRNA expression of UGN and GC-C in duodenum, jejunum and colon. The data obtained suggest that, in a mouse model of diet-induced obesity, a down-regulation of intestinal mRNA expression of GN, UGN and its GC-C receptor is accompanied by a compensatory increase of renal UGN mRNA expression. We hypothesize that the decrease in gene expression levels of intestinal GPS may contribute to the development of hypertension and obesity during hypercaloric diet intake.

Topics: Animals; Diet; Gastrointestinal Hormones; Gene Expression Profiling; Hypertension; Intestines; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Natriuretic Peptides; Real-Time Polymerase Chain Reaction