Absence of neural modulation of hypoxic pulmonary vasoconstriction in conscious dogs

Our objectives were 1) to quantify the magnitude of the hypoxic pulmonary vasoconstrictor (HPV) response in conscious dogs by utilizing pulmonary vascular pressure-cardiac index (P/Q) plots and 2) to assess the extent to which the autonomic nervous system (ANS) modulates the HPV response. Multipoint P/Q plots were constructed in conscious dogs during normoxia and during bilateral alveolar hypoxia by stepwise constriction of the thoracic inferior vena cava to reduce Q. With the ANS intact, the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) increased (P less than 0.01) approximately twofold during hypoxia over a broad range of Q. The absolute magnitude of the HPV response was related (P less than 0.01) to the level of Q. We hypothesized that if ANS activation reduces the magnitude of HPV in intact dogs, then we would expect the magnitude of HPV to be increased both after combined sympathetic alpha-(phentolamine) and beta-(propranolol) adrenergic block and after total autonomic ganglionic block (hexamethonium). A marked HPV response (P less than 0.01) was observed after both combined sympathetic block and ganglionic block over a broad range of Q during alveolar hypoxia. The magnitude of the HPV response with the ANS intact, however, was not significantly different from the magnitude of HPV after combined sympathetic block (P = 0.45) or after ganglionic block (P = 0.64) at any level of Q. Thus, during bilateral alveolar hypoxia, the ANS does not appear to attenuate the HPV response of intact conscious dogs.

Neural antagonists modulate pulmonary vascular pressure-flow plots in conscious dogs

Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed in conscious dogs during normoxia by graded constriction of the thoracic inferior vena cava to reduce Q. P/Q plots were generated with the autonomic nervous system (ANS) intact and following total autonomic ganglionic block, cholinergic block, and sympathetic alpha- and beta-adrenergic block alone and in combination. With the ANS intact, the relationship between the pulmonary vascular pressure gradient [pulmonary arterial pressure (PAP)--pulmonary capillary wedge pressure (PCWP)] and Q was linear with an extrapolated pressure intercept of 0 mmHg. Total autonomic ganglionic block increased PAP-PCWP over the entire range of Q studied (60–140 ml . min-1 . kg-1). Cholinergic block resulted in a small increase in PAP-PCWP at a Q of 60 ml . min-1 . kg-1, a small decrease in PAP-PCWP at a Q of 140 ml . min-1 . kg-1, but no change in PAP-PCWP over the midrange of Q. Sympathetic beta-adrenergic block increased, and sympathetic alpha-adrenergic block decreased PAP-PCWP over the entire range of Q studied. Combined sympathetic alpha- and beta-adrenergic block also increased PAP-PCWP at each level of Q. Thus the ANS, either directly or via circulating catecholamines, exerts an active regulatory influence on the pulmonary vascular P/Q relationship of intact conscious dogs during normoxia over a wide range of Q. Activation of sympathetic beta-adrenergic receptors results in pulmonary vasodilatation, whereas, alpha-receptor activation results in vasoconstriction. Surprisingly, based on the effects of total autonomic ganglionic block and combined sympathetic alpha- and beta-adrenergic block, the net effect of the ANS on PAP-PCWP/Q during normoxia appears to be pulmonary vasodilatation.

Vascular responses in canine subcutaneous adipose tissue to hypothalamic stimulation

The present studies investigated vascular responses to electrical stimulation of the posterior hypothalamus in isolated but perfused and innervated subcutaneous adipose tissue in adult dogs. Three groups of dogs were distinguished: in one, electrical stimulation elicited vasodilation; in another, vasoconstriction, and in a third, neither significant vasodilation nor vasoconstriction occurred. Histological examination revealed that electrode placements were in the medial posterior hypothalamus, the lateral posterior hypothalamus, and the medial septal region, respectively. Hypothalamic stimulation failed to alter concentrations of free fatty acids or glycerol in venous blood from subcutaneous fat. Local beta-adrenergic block (propranolol) reversed the vasodilation to vasoconstriction while local alpha-adrenergic block (dihydroergotamine) abolished the vaso constrictor response. These results suggest that selective stimulation of the posterior hypothalamus results in neurogenic activation of both alpha- and beta-adrenergic mechanisms in adipose tissue vasculature. beta-Adrenergic vasodilation appears to predominate if the electrode is located medially, and alpha-adrenergic vasoconstriction appears to predominate if the electrode is located in the lateral posterior hypothalamus.