PYROGENIC STIMULATION OF VASCULAR-RESISTANCE IN CONSCIOUS SHEEP

Increased arterial blood pressure following a pyrogenic reaction has b een reported in previous studies, however the mechanism of this hypert ension has not been examined in detail. The present study investigated the effects of both intravenous (IV) and intracerebroventricular (ICV ) injection of lipopolysaccharide (LPS) from E.coli on body temperatur e (Tb), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), calculated total peripheral resistance (CTPR), stroke volume (SV ) and plasma levels of adrenocorticotropin (ACTH) and arginine vasopre ssin (AVP) in conscious, chronically instrumented sheep. IV injection of LPS (1 mu g) increased Tb in a biphasic manner from 38.7+/-0.1 to 3 9.5+/-0.2 degrees C after 50 min and to 39.9+/-0.2 degrees C after 130 min, and MAP increased biphasically from 64+/-1 to 70+/-4 mmHg after 40 min and to 78+/-3 mmHg after 130 min. CO initially decreased from 4 .4+/-0.1 to 3.5+/-0.1 after 40 min followed by a secondary rise to 4.8 +/-0.1 l/min after 100 min. This occurred together with a large, bipha sic increase in CTPR from 14.5+/-1.0 to 22.0+/-2.0 mmHg/l/min at 40 mi n, and to 18.1+/-0.1 mmHg/l/min at 120 min. HR increased from 68+/-4 t o 97+/-4 b/min and SV decreased from 65+/-2 to 41+/-4 ml/beat during t he first phase of activation. Plasma ACTH increased from 22+/-9 to 104 3+/-175 pg/ml after 80 min, and plasma AVP increased from 0.7+/-0.2 to 12+/-4.0 pg/ml after 60 min. ICV injection of LPS produced a long-las ting increase in Tb and MAP, but had no effect on HR or plasma AVP. Pl asma ACTH increased from 30+/-12 to 427+/-110 pg/ml. These changes sug gest that intravenous pyrogenic infection produces a potent vasoconstr ictor action in sheep to increase blood pressure, possibly mediated by the actions of AVP within the CNS, or other pyrogenically released va soconstrictor factors. Furthermore, the duration of activation of the cardiovascular system following peripheral and central LPS administrat ion is different, which together with the contrasting effects on ACTH and AVP; indicate the involvement of several hypertensive mechanisms.