Cardiovascular adrenoreceptor balance during hemorrhagic hypotension and shock.
The primary aim of this study was to examine the hypothesis that the ability of the cardiovascular system to compensate for hemorrhagic hypotension is controlled by a balance between the relative influence of the alpha 1 and extrasynaptic alpha 2 adrenoreceptors. Previous studies have implied that, although both receptors participate in the baroreceptor response to hypotension, only the extrasynaptic alpha 2 receptors are able to maintain the compensatory vasoconstrictor effort for a prolonged period of time. In each experiment two Sprague-Dawley rats were anesthetized and subjected to a modified Wiggers hemorrhagic shock protocol. One rat in each pair was pretreated with either 25 mg/kg of the cyclooxygenase inhibitor sodium meclofenamate or 0.5 mg/kg of the selective alpha 1 antagonist prazosin. The results indicate that neither drug interfered with the normal maximum compensatory effort as defined by the maximum blood loss (ie, reduced total vascular capacitance) when mean arterial pressure (MAP) was reduced to 30 mmHg by hemorrhage. In fact, when normalized for pre-hemorrhage MAP, it was apparent that prazosin, which lowered pre-hemorrhage MAP, may have actually improved the compensatory response. Sodium meclofenamate increased the time to reach the maximum compensatory effort (comp time), while prazosin increased the time to reach 20% uptake from the blood reservoirs (decomp time). Since both drugs enhanced the total time (comp + decomp) and both are known to interfere with alpha 1 function, these studies support the hypothesis stated above.
D000818:Animals; D016861:Cyclooxygenase Inhibitors; D007022:Hypotension / Q000503:physiopathology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D011941:Receptors, Adrenergic; D008469:Meclofenamic Acid; D011224:Prazosin