Renal phosphodiesterase 4B is activated in the Dahl salt-sensitive rat.
Reduced beta-adrenoreceptor signaling is associated with increased sympathoadrenal activity in hypertensive patients and animal models of hypertension. However, the mechanism that accounts for this characteristic decline in beta-adrenergic signaling is unclear. In the present study, we investigated renal phosphodiesterase 4B, which metabolizes cAMP. Immunoblot analysis detected only the phosphodiesterase 4B4 isoform present in kidney tissue from spontaneously hypertensive rats, hypertensive Dahl salt-sensitive (SS) rats, and Dahl salt-resistant rats. The phosphorylated (activated) form of the protein was present at 2-fold greater levels in Dahl SS rats than in spontaneously hypertensive rats and Dahl salt-resistant rats, whereas the unphosphorylated form of the protein was reduced by approximately one half in SS animals. In accord with immunoblot data, rolipram-inhibitable cAMP hydrolyzing activity, a measure of PDE4 activity, was approximately 3-fold greater in kidney cytosolic extracts from SS rats than in extracts from spontaneously hypertensive rats and salt-resistant rats. Phosphodiesterase 4B expression was detected by immunohistochemistry in the renal vasculature, proximal tubules, and distal tubules. These results raise the possibility that increased PDE4 activity, specifically phosphodiesterase 4B4 activity, reduces beta-adrenergic signaling in the kidney and contributes to salt-sensitive hypertension in the Dahl SS rat.
Tawar
Urmila
U
Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Kotlo
Kumar
K
Jain
Shilpa
S
Shukla
Sagar
S
Setty
Suman
S
Danziger
Robert S
RS
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation; D006977:Hypertension, Renal / Q000201:enzymology* / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000201:enzymology*; D007684:Kidney Tubules / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D020303:Rats, Inbred Dahl / Q000378:metabolism*; D011918:Rats, Inbred SHR; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D007527:Isoenzymes; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4