Relationship between the chemical structure of prostaglandins and their vasoactivities in dogs

Abstract

1 The relationship between the chemical structure and the direct vasoactivity of different prostaglandins administered intra-arterially was studied in the dog hindlimb preparation. 2 All of the prostaglandins studied, except PGF_1α and PGF_2α, caused a dose related decrease in the femoral arterial perfusion pressure in dogs in which the femoral arterial blood flow was kept constant, indicating the direct vasodilator action of these prostaglandins. 3 Among the prostaglandins studied, PGE₁ is the most potent vasodilator. Comparing the chemical structure and vasodilator action of PGE₁ with those of different prostaglandins, the following conclusions can be made: 4 The formation of the Δ⁵ double bond in PGE₁ causes no change in its vasodilator activity, whereas the saturation of the Δ¹³ double bond of PGE₁ slightly reduces its activity. 5 The alterations in the orientation and length of the carboxyl and alkyl side chains reduce markedly the vasodilator action of PGE- and PGA-compounds. 6 The presence of a carbonyl group at C9 is the most important requirement for the potent vasodilator action of PGE₁. On the other hand, the presence and S-configuration of a hydroxyl group at C15 are essential for the intrinsic action at the receptor sites in the vascular smooth muscle, but may not be responsible for the vasodilator action. 7 The esterification of PGE₁ or PGE₂ and a triple bond formation and the replacement of C7 with oxygen in prostaglandin appear to reduce or abolish their vasodilator action.