Transient effects of histamine on the capillary filtration coefficient

Abstract

The duration of the effect of histamine to increase the capillary filtration coefficient (CFC) was evaluated in isolated, denervated canine forelimb, hindpaw, and gracilis muscle. CFC was estimated at timed intervals during local intraarterial histamine (12 μg base·min −1 per 100 ml·min −1 blood flow). Propranolol (3 mg/kg) was administered to inhibit possible catecholamine-mediated inhibition of histamine-induced increases in CFC. The increase in CFC was greatest after 10 min of drug infusion and returned to control values after 25 min of histamine. These data indicate that the effect of histamine to increase CFC is highly transient. The relative contributions of increases in surface area and/or permeability to increases in CFC were assessed by maximally dilating the vasculatures of the three tissues with nitroprusside (increasing surface area to a maximum). Any further increase in CFC produced by combined nitroprusside-histamine infusion would then be due to increased permeability. Histamine, when infused concomitantly with nitroprusside, produced further increases in CFC relative to CFC obtained during infusion of nitroprusside alone. The time course for the transient increase in CFC during combined histamine-nitroprusside infusion was similar to the time course during histamine alone. These data suggest that the transient increase in CFC induced by histamine is primarily mediated by a transient increase in microvascular permeability to fluid in all three tissues. The transient nature of this increase in permeability was probably not related to a β-antagonistic action of the catecholamines (which may have been increased reflexly) because these tissues were β-blocked with propranolol. An equation was derived to estimate the ratio of the number of gaps which form between venular endothelial cells to the number of small pores. It was concluded that less than 3% of small pores need increase in radius to form large pores or gaps with radii ranging from 195 to 1000 Å to explain the increases in CFC demonstrated in the hindpaw and gracilis muscle and that structures beyond the microvascular endothelium may provide the principle resistance to fluid efflux during histamine.