ENDOGENOUS VASOCONSTRICTOR TONE IN INTESTINE OF NORMAL AND PORTAL HYPERTENSIVE RATS

The purpose of the present study was to determine the effects of endogenous norepinephrine, vasopressin (AVP), and angiotensin II (ANG II) on normal intestinal microvascular dimensions and to determine whether endogenous vasoconstrictor tone was altered in chronic portal hypertension. The intestine of normal and portal hypertensive rats was prepared for in vivo microscopic observation, and an arteriole (1A, 2A, or 3A) was selected for study. Arteriolar diameter and erythrocyte velocity were continuously monitored and used in the calculation of arteriolar blood flow. Once steady-state conditions were established, specific antagonists to alpha-adrenergic, AVP, or ANG II receptors were applied locally to remove the influences of each of these systems. In normal animals, blockade of alpha-adrenergic receptors produced a 1.3, 1.5, and 14.7% increase in the diameter of 1A, 2A, and 3A, respectively. AVP blockade in normal animals produced an 8.7,1.6, and 1.5% increase in the diameter of 1A, 2A, and 3A, respectively; ANG II blockade only produced an increase in 3A diameter (5.8%). alpha-Adrenergic blockade produced a smaller increase in portal hypertensive 3A diameter (2.3%) compared with normal rats. AVP and ANG II blockade produced a significantly larger dilation of 3A (AVP, 4.8%) and 1A (ANG II, 3.8%), respectively, compared with control. Plasma AVP and ANG II levels were higher in portal hypertensive (AVP, 9.1 pg/ml; ANG 11, 8.6 pg/ml) than in normal rats (AVP, 5.5 pg/ml; ANG II, 6.6 pg/ml). The results of the present study indicate that 1) alpha-adrenergic and AVP activity accounts for the majority of extrinsic vasoconstrictor tone in the normal intestine and 2) AVP and ANG II account for the majority of extrinsic vasoconstrictor tone in the portal hypertensive intestine. Furthermore, the data suggest that elevations in AVP and ANG II levels may partially offset the loss of adrenergic vasoconstrictor tone in portal hypertension.