VASCULAR NE RESPONSIVENESS IN PORTAL-HYPERTENSION - ROLE OF PORTAL PRESSURE AND PORTOSYSTEMIC SHUNTING

Previous studies have suggested that the development of portal venous collaterals and subsequent portosystemic shunting is the key event res ponsible for the reduced vasoconstrictor effectiveness in chronic port al hypertension. The purpose of the present study was to test this hyp othesis. Thirty-nine male Sprague-Dawley rats were divided into four g roups: end-to-side portacaval shunt (PCS, n = 11), chronic prehepatic portal hypertension (CPH, n = 10), acute prehepatic portal hypertensio n (APH, n = 8), and sham-operated controls (Sham, n = 10). The small i ntestine was prepared for microcirculatory studies. First-order arteri olar diameter and erythrocyte velocity were measured on-line, and bloo d flow was subsequently calculated. Once steady-state values were obta ined the preparation was topically exposed to incremental doses of nor epinephrine. The half-maximal effective dosage (ED(50)) for maximal va soconstriction (diameter response) was significantly increased in PCS (4.5 mu M) and CPH (1.5 mu M) compared with Sham (0.8 mu M). However, the ED(50) was significantly lower in APH (0.17 mu M) than in Sham. Si milarly the ED(50) for maximal blood flow reduction was higher in PCS (2.4 mu M) and CPH (1.2 mu M) compared with Sham (0.2 mu M). The resul ts demonstrate that vascular norepinephrine responsiveness is reduced in both portacaval shunted and chronic portal hypertensive rats, but n ot in acute portal hypertension. These data indicate that portosystemi c shunting, not portal pressure elevation, is the key event leading to the reduced vascular norepinephrine responsiveness observed in CPH co nditions.