Pharmacological manipulation of cardiovascular responses to lower body negative pressure

To evaluate influences on blood volume distribution, atrial natriuretic peptide concentrations (ANP) and thoracic and leg electrical impedance at 2.5 (TI2.5 and LI2.5, respectively) and 100 kHz (TI100 and LI100, respectively) were monitored during administration of ketanserin, noradrenaline and trimetaphan combined with lower body negative pressure (LBNP) in 12 subjects. Administration of clinically relevant doses of ketanserin alone did not induce changes in mean arterial pressure (MAP) or in the central blood volume, as electrical impedance and ANP concentrations did not change. During continued infusion of ketanserin an increase in MAP from a mean of 90 (range 83-108) to 113 (range 98-138) mmHg was induced by noradrenaline, but TI2.5 [mean 45.6 (range 39.3-54.2)] and TI100 [mean 33.8 (range 27.5-38.5) omega] remainded stable until ganglionic blockade and LBNP were applied, when they increased by a mean of 3.1 (range 2.0-6.1) and 2.7 (range 1.1-4.2) omega, respectively (P < 0.05). Conversely, LI2.5 [mean 79.6 (range 74.1-89.4)] and LI100 [mean 56.7 (range 52.4-63.3) omega] decreased by a mean of 3.2 (range 1.2-8.0) and 2.3 (range 0.9-3.9) omega, ANP from a mean of 27.7 (range 10.2-62.7) to 12.7 (range 7.1-27.5) pmol.l-1 and MAP fell to a mean of 62 (range 42-70) mmHg (P < 0.05). The heart rate was a mean of 75 (range 69-77) beats.min-1 and did not change until LBNP, when it increased to a mean of 102 (range 78-104) beats.min-1, as presyncopal symptoms appeared. The data indicated that serotonergic blockade by ketanserin and alpha-sympathetic stimulation by noradrenaline did not affect blood volume distribution in normal humans, but that ganglionic blockade combined with LBNP reduced the central blood volume as leg volume increased; during central hypovolaemia tachycardia induced by ganglionic blockade did not prevent the fall in MAP, and thereby the appearance of presyncopal symptoms.