Adrenergic regulation of total systemic distensibility. Venous distensibility effects of norepinephrine and isoproterenol before and after selective adrenergic blockade

The extracardiac factors that influence cardiac performance are arterial pressure and the venous return of blood to the heart. Venous return is influenced by the capacity and the distensibility characteristics of the peripheral capacitance vasculature. Distensibility determines the extent to which venous pressure increases and hence the extent to which venous return and cardiac performance increase when volume is added rapidly to the intravascular space. Thus an understanding of vascular distensibility is important to an understanding of integrated cardiovascular function. Because the influence of selective alpha and beta adrenergic receptor stimulation on total vascular distensibility is not well understood, the present study was undertaken to examine the distensibility effects of norepinephrine and isoproterenol before and after selective adrenergic receptor blockade. Fifty-one dogs were anesthetized, subjected to ganglionic block and placed on cardiopulmonary bypass at 1.5 liters/min. The reciprocal of distensibility or compliance was determined by sudden, transient occlusion of venous return and observation of the increase in central venous pressure (CVP) after a given amount of blood volume was added to the circulation (ΔCVP/83 ml). Norepinephrine, 30 μg/min, and isoproterenol, 6 μg/min, were each infused for 24 minutes. Norepinephrine was associated with an initial, transient (2 minute) increase in ΔCVP/83 ml of 18 ± 3 percent (mean ± standard error of the mean) (p < 0.001) above a control level of 16.9 ± 0.9 cm H₂O/83 ml, followed by a sustained decrease of 7 ± 3 percent (p < 0.05) below control level. Isoproterenol was associated with a decrease, which was both initial and sustained, in ΔCVP/83 ml of 19 ± 3 percent (p < 0.001) below a control level of 17.5 ± 1.0 cm H₂O/83 ml. Selective blockade with phenoxybenzamine and propranolol revealed that the norepinephrine effect was mediated almost entirely through alpha adrenergic receptor stimulation and the isoproterenol effect mostly through beta adrenergic stimulation. Thus alpha and beta adrenergic receptor stimulation with norepinephrine and isoproterenol, respectively, is associated with sustained increases in total systemic vascular distensibility and would be expected to be associated with diminished increases in venous pressure, venous return and cardiac performance when a given amount of volume is added to the intravascular space.