Adrenergic responsiveness of isolated saphenous arterial segments during hypovolemic hypotension and shock

Previous studies from this laboratory suggest that cutaneous vasculature responds to hypovolemic hypotension by constriction as a direct result of catecholamine interaction with alpha-receptors (A.J.P. 212:488, 1967; A.J.P. 219:1210, 1970). The objectives of the present study were to determine if the effective smooth muscle population or adrenergic innervation densities varied as the dog progressively moves from reversible to irreversible hemorrhagic shock. Saphenous arteries were removed with adventitia intact during various stages of shock and placed in an isolated tissue chamber filled with warm (37 degrees C) Krebs-Henseleit solution bubbled with 95% O2 and 5% CO2. Norepinephrine (NE) dose-response curves and periarterial electrical stimulation (ES) response studies were conducted. The maximum responses to NE which we consider to represent an index of effective physiological smooth muscle population and ES (ie, effective physiological innervation density) decreased slightly during the progression from control Stage I to Stage III shock. The sensitivity of the innervated alpha-receptors as measured by the ES necessary to obtain a 50% maximal response (ES50) did not change during any stage of shock, indicating normal neural function. However, a significant reduction in NE ED50 from a control of 1.9 +/- 0.3 microM to 1.2 +/- 0.1 microM during early compensatory shock which persisted through early normovolemic shock indicated augmentation of alpha-receptor sensitivity. Signs of alpha-receptor desensitivation did not appear until late in the irreversible shock process when the NE ED50 increased to 3.9 +/- 1.1 microM.