EFFECTS OF REGITINE (C-7337) UPON THE BLOOD FLOW RESPONSES TO EPINEPHRINE IN THE INNERVATED HIND LIMB OF THE DOG

¹ Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest College, Winston-Salem, North Carolina

Measurements of the femoral arterial blood flow and lateral pressure in the innervated hind limb of a dog were used to evaluate peripheral vascular effects of Regitine.

In these studies control injections of 0.08 microgm. of methacholine increased flow to 192 per cent of the control flow; 1 microgm. of epinephrine per se decreased flow to 45 per cent of the control flow.

The usual contour of the flow response to epinephrine was a rapid decrease in flow followed by a gradual return to the control value. This was often followed by a phase of slightly increased flow. Variations from this contour noted in the literature and described in this paper were probably due to the presence of pyrogenic substances in the epinephrine solution.

A variable increase in femoral arterial flow and decrease in peripheral resistance followed femoral arterial injections of Regitine per se. The magnitude of the response was not significantly different for doses of 0.015, 0.1, and 0.15 mgm./kgm. and could not be correlated with the control blood pressure, blood flow, heart rate, the size of the dog, or the control response to methacholine and epinephrine. The average response to all doses was an increase to 170 per cent of control flow.

A total dose of 1.7 mgm. of Regitine or more (0.1 to 0.15 mmg./kgm.) was required to block completely the constrictor response to 1 microgm. of epinephrine. After such dose, 1 microgm. of epinephrine caused immediate vasodilation, the flow increasing on the average to 188 per cent of the control flow. The responses to epinephrine usually had returned to the control constrictor responses by four hours after the Regitine. The response to 1 microgm. of epinephrine was kept constant by small infusions of Regitine. Under these conditions, 0.25 to 0.5 microgm. of epinephrine produced dilation to a lesser degree than 1 microgm.; 5 to 10 microgm. gives a greater dilation than 1 microgm. and doses of over 10 microgm. of epinephrine give an intense constriction followed by a prolonged dilation.

Regitine dissolved in 100 ml. of saline given to dogs over a period of half an hour in doses up to 19 mgm./kgm. or a total cumulative dose of up to 32 mgm./kgm. given over two and one-half hours produced no noticeable toxic symptoms except tachycardia and a quieting effect.

Regitine appears to be an effective anticonstrictor agent to epinephrine in about one-fifth to one-seventh the dose of Ro 2-3248, or of Priscoline.