Decreased expression of natriuretic peptide A receptors and decreased cGMP production in the choroid plexus of spontaneously hypertensive rats.
Atrial natriuretic peptide receptor (ANP) subtypes and their signal transduction response were characterized in choroid plexus of spontaneously hypertensive (SHR) and normotensive (WKY) rats. We found two ANP receptor subtypes, guanylate cyclase coupled and uncoupled, in both rat strains. Binding of ANP was lower in SHR choroid plexus when compared to WKY. The lower ANP binding in SHR was the result of a decrease of binding to the guanylate cyclase-coupled receptor subtype A, a decrease that correlated well with the decreased ANP-induced cGMP formation in SHR. Forskolin stimulated cGMP production to the same extent in both strains. In WKY rats, ANP increased basal and forskolin-stimulated cAMP production; conversely, in SHR, ANP did not affect the basal level of cAMP and inhibited the forskolin-stimulated cAMP production. These results demonstrate differences in ANP receptor subtype expression, and ANP signal transduction in choroid plexus of hypertensive and normotensive rats, which is of possible significance to the central mechanisms of blood pressure control.
Zorad
S
S
Section on Pharmacology, National Institute of Mental Health, Bethesda, MD 20892-1264, USA.
Alsasua
A
A
Saavedra
J M
JM
D000818:Animals; D001345:Autoradiography; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology
D000242:Cyclic AMP; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP