Increased oxidative stress in renal proximal tubules of the spontaneously hypertensive rat: a mechanism for defective dopamine D-1A receptor G-protein coupling

Aim Defective dopamine D-1A dopamine receptor/ G-protein coupling has been demonstrated in renal proximal tubules of the spontaneously hypertensive ra t (SHR). In the present study, we aimed to analyze the underlying mechanism s through which such defects are introduced into the D-1A receptor protein of SHR. Materials and methods The oxidative state of SHR proximal tubules was analy zed by measuring lipid peroxidation, D-1A receptor/G-protein coupling was m easured following the induction of oxidative stress in normotensive Wistar- Kyoto (WKY) rats. Results For the first time, an increased state of oxidative stress was demo nstrated in SHR proximal tubules compared with those of normotensive contro ls, WKY and Sprague-Dawley rats. Lipid peroxidation levels in SHR were sign ificantly higher by 66 and 79%, relative to WKY or Sprague-Dawley rats, res pectively. Hydrogen peroxide treatment of proximal tubules from SHR, WKY an d Sprague-Dawley rats induced an additional increase in lipid peroxidation in a dose-dependent manner, although the percentage induction was fewer in SHR than in WKY and Sprague-Dawley rats. This induction of lipid peroxidati on in WKY rats resulted in a loss of D-1A/G-protein coupling, with no decre ase in receptor protein. Treatment of WKY rat proximal tubules with an anti oxidant, ascorbic acid, or a reducing agent, dithiothreitol, induced D-1A r eceptor/G-protein coupling. Conclusions These data indicate that D-1A receptor/G-protein coupling is mo dulated by changes in redox states. Therefore, the D-1A receptor/G-protein coupling in SHR may have been damaged by reactive oxygen species released a s a result of the elevated oxidative stress seen in the proximal tubules. J Hypertens 1998, 16:1659-1665 (C) Lippincott Williams & Wilkins.