Dissociation of natriuresis and diuresis and heterogeneity of the effector system of atrial natriuretic factor in rats
| Autor: | Pavel Hamet, R Garcia, R C Willenbrock, Johanne Tremblay |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1989 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Diuresis Natriuresis Vasodilation Kidney Muscle Smooth Vascular chemistry.chemical_compound Internal medicine Extracellular medicine otorhinolaryngologic diseases Animals Cyclic guanosine monophosphate Cyclic GMP Rats Inbred Strains General Medicine NPR1 Rats Endocrinology medicine.anatomical_structure chemistry Diuretic Atrial Natriuretic Factor Research Article |
| Popis: | The hypotensive, natriuretic, and diuretic actions of human atrial natriuretic factor-(99-126) (hANF) are accompanied by an elevation of cyclic guanosine monophosphate (cGMP) in plasma and urine. However, the oxidized hANF analogue, human [Met-O110]ANF-(99-126) (Met-O-ANF), has been reported to be unable to increase cGMP (Biochem. Biophys. Res. Commun. 128: 538-546). We employed this oxidized peptide to evaluate the relationship between its biological effects and cGMP generation, with cGMP serving as a marker of the recognized property of ANF to stimulate particulate guanylate cyclase. Met-O-ANF appeared to be a partial agonist, exhibiting a decreasing order of relative potency of hypotensive, vasorelaxant, diuretic, and natriuretic functions compared to hANF. A lower degree of cGMP increases was achieved by this analogue in cultured smooth muscle and endothelial cells. Met-O-ANF doses, which led to a significant increase in diuresis, were neither natriuretic nor accompanied by an increase of urinary cGMP. We were thus able to dissociate the diuretic and natriuretic effects of ANF. High doses of the oxidized analogue were required to elevate cGMP levels in plasma and urine. In isolated kidney fractions, Met-O-ANF's action on cGMP was significantly lower in glomeruli (fivefold less), virtually absent in the collecting duct, yet only slightly different (20% less) in thick ascending limb. Our results indicate that the diuretic and natriuretic effects are exerted at distinct sites, with only the natriuresis being related to an increase of extracellular cGMP. The variability of differential potency of biological and biochemical effects from tissue to tissue of these two forms of human ANF support the notion of the heterogeneity of the ANF effector system. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|