Prostaglandin B ₂ -Induced Cutaneous Vasoconstriction of the Canine Hind Paw

Abstract

The cutaneous vascular effects of prostaglandin B 2 (PGB2) were studied in dogs during constant-flow perfusion of the hind paw. The effects of PGB 2 (50-800 ng/kg min" 1 , ia) on systemic pressure, hind-paw perfusion pressure, and responses to local heating at 45°C (30 seconds) and cooling at 4°C (90 seconds) were measured in 44 dogs. PGB 2 increased perfusion pressure by 50 ± 19 mm Hg to 218 ± 21 mm Hg without any effect on systemic arterial blood pressure. The pressor response to cooling increased from 34 mm Hg to 53 mm Hg (50 ng/kg min~1PGB 2 ), but the dilator response to heating was reduced significantly during infusions of PGB 2 (50 and 100 ng/kg). Acute denervation and reserpine treatment (0.5 mg/kg dog" 1 for 2 days) reduced the constrictor responses to PGB 2 . The abilities of PGB 2 to produce intense vasoconstriction, which is blocked by acute denervation and reserpine, to enhance responses to cooling, and to antagonize responses to heating make this preparation a useful model for the study of Raynaud's phenomenon and suggest that a prostaglandin, perhaps PGB 2 , may participate in cutaneous vasospastic disorders. KEY WORDSRaynaud's phenomenon cold-induced vasoconstriction enhanced by PGB 2 heat-induced vasodilation antagonized by PGB 2 skin blood flow denervation reserpine pressor response • Recent reports from our laboratory (1-3) that have been confirmed by Joiner and co-workers (4) have demonstrated that prostaglandin B 2 (PGB 2 ) is a potent, fairly selective constrictor of the canine cutaneous and pulmonary vasculature with only slight systemic vasodilator or vasoconstrictor activity. Also, it has been suggested that PGB compounds mediate the formation of cutaneous ulcerative lesions (5) and constrict human hand veins (6). Therefore, we evaluated PGB 2 -induced vasoconstriction as a possible model for Raynaud's phenomenon.

Lack of Correlation Between Initial Vascular Resistance and Responses to Vasoconstrictor Stimuli in the Perfused Canine Hindpaw

“…This procedure also reduces the pressor response to prostaglandin B, (28) and prostaglandin F,, (29). The constrictor response to these agents is dependent on tonic sympathetic impulse activity to the canine paw.…”

Contractile physiology and response to temperature changes of the tunica dartos muscle of the rat

“…Rightmost bar is the response to a decrease in temperature after the drug had been flushed from the bath (C2), expressed as a percentage of C1. Bars show mean ± SEM production of prostaglandins [5]. The contraction to cooling of the dartos muscle with skin was not inhibited by the cyclooxygenase inhibitor, indomethacin, and so we conclude that the mediator is not prostaglandin or any other product of the cyclooxygenase cascade.…”

Enhancement of Neural and Thermal Vasoconstriction by Prostaglandin B1

“…Recent reports from our laboratory demonstrated that prostaglandin B2 (PGB2) enhanced the constrictor response of the perfused canine paw to both sympathetic nerve stimulation and local cooling while antagonizing the vasodilator response to local heating (1,2). These effects were manifested at concentrations of PGB2 that profoundly constricted the canine paw.…”

“…It was suggested that the ability of PGB2 to enhance thermal and neurogenic vasoconstriction resulted from a selective ability of PGB compounds to facilitate catecholamine release. However, the possibility that these effects of PGB, were secondary to the increased wall stress resulting from the higher distending pressure could not be entirely eliminated (1)(2)(3).…”

“…Prostaglandin B1 (PGB1) is less potent a constrictor of the canine paw than is PGB2 and possesses intrinsic vasodilator properties at low concentrations (1)(2)(3). This study examines the effects of PGBl on the responses of the perfused canine paw to local cooling and heating to evaluate whether the effects of PGB compounds on these interventions are intrinsic to the prostaglandin B molecule or reflect the increased wall stress and transmural pressure associated with the constricted paw.…”