Effects of vasoactive agents in healthy and diseased human saphenous veins

Smooth muscle reactivity is one of the factors involved in the pathogenesis of varicose veins. We investigated the myotropic effects of the 3 main vasoconstrictor agents norepinephrine (NE), angiotensin II (Ang II), and endothelin-1 (ET-1) in isolated human saphenous veins.

Human saphenous veins were collected from 23 patients with primary chronic venous insufficiency who underwent elective varicose vein resections and who were stratified into the following 3 groups: group 1, 7 patients in clinical class 2; group 2, 9 patients in clinical classes 3 and 4; and group 3, 7 patients in clinical classes 5 and 6. Moreover, 6 patients who underwent arterial bypass grafting procedures represented the control group. The tissues were suspended in organ baths that contained Krebs solution, and their mechanical responses were measured isometrically. The cumulative concentration-response curves to Ang II, NE, and ET-1 were performed at 90-minute intervals in each tissue.

In the control tissues, NE, Ang II, and ET-1 induced concentration-dependent contractions with apparent affinities (pEC50, the negative logarithm to base 10 of the molar concentration of the agonist, which produces the 50% of the maximal effect) and maximal effects (maximum effect, g of contraction) that were equal to 7.06 +/- 0.23, 8.53 +/- 0.34, 7.63 +/- 0.10, and 2.21 +/- 0.33, 1.65 +/- 0.31, 2.60 +/- 0.77, respectively. Two main findings were evident in comparison of varicose veins with control tissues. First, the maximum effect that was evoked by all of the stimulants was reduced progressively with the increasing severity of the disease, which raised the third group to statistical significance for both NE and Ang II (P <.05). Second, a marked reduction of Ang II apparent affinity was already evident in tissues that were taken from patients in an early stage of the disease (P <.05).

The demonstration of a significant reduction in Ang II and NE contractile activities and the important reduction of that of ET-1 in the diseased veins as compared with the control tissues extends the previous observations regarding the impairment of smooth muscle contractility in primary chronic venous insufficiency. Moreover, the dramatic reduction of Ang II affinity, which appears in an early stage of the disease, supports the hypothesis that such abnormality within the venous wall could play a role in the pathogenesis of primary varicose vein disease.