No abstract

ANP steady-state mRNA increases in extracardiac (i.e., stomach antrum) tissue as well as in the ventricle of the heart in CHF. The product of the ANP gene expression, i.e., the ANP prohormone is the same in the extracardiac tissues as within the heart. Whether the increased extracardiac ANP steady-state mRNA and its resultant increased atrial natriuretic peptides helps prevent bowel wall edema in CHF needs to be elucidated.

Glibenclamide enhanced the activity in the rat of guanylate cyclase in a number of extra-pancreatic tissues. Thus, glibenclamide enhanced guanylate cyclase activity in vitro two- to threefold in liver, kidney, heart, spleen and colon at a concentration of 1 mumol/l. Dose-response curves of glibenclamide on hepatic guanylate cyclase revealed that more than half-maximal stimulation was observed at a concentration as low as 10 nmol/l (p less than 0.001) and no stimulation of guanylate cyclase was seen when the concentration was decreased to 1 nmol/l. Maximal enhancement was seen at 100 nmol/l of glibenclamide. Varying the concentration of the guanylate cyclase co-factor manganese had no effect on the glibenclamide enhancement of guanylate cyclase. In addition to the increased insulin receptors found recently in monocytes and fibroblasts, the present findings may help explain the extra-pancreatic effects of glibenclamide and possibly of other sulphonylurea drugs.

Circadian variation in the circulating concentrations of the N-terminal and C-terminal portions of the atrial natriuretic factor prohormone (pro ANF) was evaluated in 8 men, ages 41-47, who have been followed for 19 years with respect to circadian variation in physiological variables including blood pressure and clinical chemistries. The N-terminus of the ANF prohormone contains two peptides consisting of amino acids 1-30 and 31-67 while the C-terminus contains 1 peptide (amino acids 99-126) of this 126 amino acid prohormone which lower blood pressure and have natriuretic properties. To determine if either the N-terminus and/or the C-terminus of the prohormone have a circadian variation in their circulating plasma concentrations these 8 men had blood samples obtained for radiommunoassay every 3 hr during a 24-hr period. Three radiommunoassays which immunologically recognize (1) the whole N-terminus (i.e. amino acids 1-98), (2) the midportion of the N-terminus (amino acids 31-67) and (3) the C-terminus (amino acids 99-126) of the ANF prohormone were utilized. The whole N-terminus, the midportion of the N-terminus which circulates after being proteolytically cleaved from the rest of the N-terminus, and the C-terminus each had a peak circulating concentration between 0400 and 0700 which were significantly (P less than 0.001) higher than their concentrations at any other time throughout the 24-hr period.(ABSTRACT TRUNCATED AT 250 WORDS)