ENDOGENOUS VASOPRESSIN SUPPORTS BLOOD-PRESSURE AND PREVENTS SEVERE HYPOTENSION DURING EPIDURAL-ANESTHESIA IN CONSCIOUS DOGS

To evaluate whether, and to what extent, release of endogenous vasopressin supports blood pressure when efferent sympathetic drive is blocked by epidural anesthesia, the authors studied the effects of high epidural anesthesia alone and when vasopressin was prevented from acting at its vascular (V1)-receptor in six awake, trained, unsedated dogs. On different days, the same dose of 0.5% bupivacaine (8-13 ml) was injected epidurally in a randomized fashion either in the presence or absence of (V1)-vasopressin receptor blockade, and the effefcts were evaluated on cardiovascular (arterial blood pressure, heart rate) and respiratory (blood gases, oxygen consumption) variables, and on plasma concentrations of vasopressin and renin. Results were also contrasted to those obtained after epidural injection of saline alone (placebo) in the same dogs. When endogenous vasopressin was prevented from acting by intravenous pretreatment with a specific V1-receptor antagonist (β-mercapto-β, β-cyclopentamethylene-propionyl-O-Me-Tyr-Arg-Vasopressin), epidural anesthesia resulted in a rapid and sustained 35% decrease in mean arterial blood pressure from 92 mmHg ± 5 SE to 60 mmHg ± 4. In contrast, only a 14% decrease in mean blood pressure from 92 mmHg ± 5 to 79 mmHg ± 6 was noted after epidural anesthesia alone. This difference between groups was statistically significant (P = 0.0001). The V1-receptor blockade alone had no detectable effect. Vasopressin plasma concentrations significantly increased from 3.4 ± 0.3 pg · ml-1 to 16.2 ± 3.2 pg · ml-1 after epidural anesthesia but did not change after epidural saline. Renin activity did not change significantly in any group despite the marked hypotension observed after combined sympathetic and vasopressin blockade. Thus, in awake, unsedated dogs, blockade of most, if not all, efferent sympathetic drive by epidural anesthesia 1) is associated with hemodynamically effective increases in vasopressin concentrations, most likely to compensate for decreased cardiac filling or arterial pressure, and induces severe hypotension when endogenous vasopressin is prevented from acting at its V1-receptor; and 2) suppresses the neurally mediated renin release known to occur in response to hypotension. The authors conclude that among the hormonal systems that can support arterial pressure, an intact vasopressin system plays an important role when spinal sympathetic outflow is selectively and markedly attenuated by high epidural anesthesia.