Blunted Beta Adrenergic Responsiveness in Prenatally Stressed Rats

Abstract

We previously reported a significant decrease in percentage fractional shortening (%FS) in pre-natally stressed rats (PS) + restraint (R) compared with the non pre-natally stressed rats (C) + R (45.8¡À3.9 vs 61.9¡À2.4 %FS; n=12; p<0.01) by echocardiography in anesthetized rats. No differences in %FS were noted between PS + R vs C without R. We now report a defect in beta adrenergic responsiveness in PS + R compared with C without R. In vivo hemodynamics were measured in awake rats using polyurethane tubing inserted percutaneously into the left ventricle and the right femoral artery. Drugs were administered through a right external jugular vein catheter. PS + R had increased heart rates and mean blood pressures compared with age and sex matched C without R (412¡À22 bpm vs 374¡À14 bpm; n=6–8; p<0.01) (134.6¡À6.1 vs 117.0¡À5.1 mmHg; p<0.01). There was no significant difference in positive and negative left ventricular dp/dt between PS + R and C without R (12297¡À328 vs 11557¡À998 +dp/dt mmHg/s; 9572¡À396 vs 9385 ¡À 862 ¨Cdp/dt mmHg/s; n=6–8; p>0.5). However, PS + R had a significantly diminished negative left ventricular dp/dt in response to increasing doses (from 25 to 400 ng/kg) of isoproterenol vs C without R (9511¡À981 vs10771¡À423; 10015¡À1137 vs 11552¡À396; 9589¡À1402 vs 12170¡À159; 10030¡À1375 vs 12098¡À408; 10704¡À1363 vs 12556¡À485 ¨Cdp/dt mmHg; n=6–8; p<0.01). We conclude that PS + R affects beta adrenergic signaling in vivo.