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 responsible for the reduced vasoconstrictor effectiveness in chronic portal hypertension. The purpose of the present study was to test this hypothesis. Thirty-nine male Sprague-Dawley rats were divided into four groups: end-to-side portacaval shunt (PCS, n = 11), chronic prehepatic portal hypertension (CPH, n = 10), acute prehepatic portal hypertension (APH, n = 8), and sham-operated controls (Sham, n = 10). The small intestine was prepared for microcirculatory studies. First-order arteriolar diameter and erythrocyte velocity were measured on-line, and blood flow was subsequently calculated. Once steady-state values were obtained the preparation was topically exposed to incremental doses of norepinephrine. The half-maximal effective dosage (ED50) for maximal vasoconstriction (diameter response) was significantly increased in PCS (4.5 microM) and CPH (1.5 microM) compared with Sham (0.8 microM). However, the ED50 was significantly lower in APH (0.17 microM) than in Sham. Similarly the ED50 for maximal blood flow reduction was higher in PCS (2.4 microM) and CPH (1.2 microM) compared with Sham (0.2 microM). The results demonstrate that vascular norepinephrine responsiveness is reduced in both portacaval shunted and chronic portal hypertensive rats, but not in acute portal hypertension. These data indicate that portosystemic shunting, not portal pressure elevation, is the key event leading to the reduced vascular norepinephrine responsiveness observed in CPH conditions.
Wu
Z Y
ZY
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130.
Benoit
J N
JN
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure; D001808:Blood Vessels / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D006975:Hypertension, Portal / Q000097:blood / Q000503:physiopathology*; D007422:Intestines / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D011170:Portasystemic Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction
D009638:Norepinephrine