Aortic vascular and atrial responses to (±)‐1‐O‐octadecyl‐2‐acetyl‐glyceryl‐3‐phosphorylcholine

Abstract

The effects of (±)‐1‐O‐octadecyl‐2‐acetyl‐glyceryl‐3‐phosphorylcholine (octadecyl‐AGPC) were studied in three types of aortic vascular smooth muscle preparations, namely, strips, rubbed and unrubbed rings, and an atrial preparation in normotensive rats. In the resting tension state, octadecyl‐AGPC did not elicit significant contractions in either rubbed or unrubbed ring preparations at concentrations lower than 1 × 10−4m. However, at a concentration of 3 × 10−4 m, octadecyl‐AGPC markedly contracted both types of ring preparations. This contractile response was partially antagonized by pretreatment with reserpine and completely blocked by phentolamine (1 × 10−6m). In preparations contracted with noradrenaline (NA), octadecyl‐AGPC elicited biphasic responses in intact ring preparations; an initial relaxation followed by contraction. Octadecyl‐AGPC induced only a slight contraction in strips and a slight relaxation in the rubbed ring preparation. Octadecyl‐AGPC did not elicit any significant effect on chronotropy or inotropy at concentrations up to 3 × 10−5 m. When the concentration was 1 × 10−4 m, octadecyl‐AGPC produced significant positive chronotropic and inotropic effects on spontaneously beating right and electrically driven left atrial preparations, respectively. Both effects were blocked by propranolol (5 × 10−8m); reserpine pretreatment antagonized only the chronotropic response. In [3H]‐dihydroalprenolol ([3H]‐DHA) binding studies, octadecyl‐AGPC had a Kd of 427.85 μm and thus was much less potent than isoprenaline (Kd = 465.10 nm) or propranolol (Kd = 4.4 nm) in displacing [3H]‐DHA in rat cardiac membrane preparations. In conclusion, relaxation and contraction induced by octadecyl‐AGPC in aortic preparations is an indirect rather than a direct effect. An unknown factor released from endothelial cells is responsible for aortic smooth muscle relaxation by octadecyl‐AGPC while released NA appears to be responsible for aortic vascular contraction and for the positive chronotropic and inotropic effects in the atrial preparations.

Antagonism of vasoconstriction induced by platelet‐activating factor in guinea‐pig perfused hearts by selective platelet‐activating factor receptor antagonists

“…The nature of this latter action is unknown. However, there is considerable evidence that Paf, at concentrations relevant to inflammation, does not exert direct effects on vascular and other types ofsmooth muscle (Cervoni et al, 1983;Lefer et al, 1984a). Thus, a further secondary mediator of coronary vasoconstriction may be released by Paf.…”

Role of Platelet-Activating Factor in Cardiovascular Pathophysiology

“…A direct stimulation of venular and endothelial cells was suggested. The effect of PAF on microcirculation has been studied also on the hamster cheek pouch (89,119). Vasoconstriction was the predominant vasomotor response to PAF.…”

Electrophysiological effects of acetyl glyceryl ether phosphorylcholine on cardiac tissues: comparison with lysophosphatidylcholine and long chain acyl carnitine

“…Levi et al (1984) demonstrated that AGEPC in concentrations of 1O-1-1O-M produced a slight negative inotropic effect in guinea-pig isolated left atria and papillary muscles. On the contrary, a positive inotropic effect of AGEPC at a concentration of l0-4 M in rat atria was reported from two laboratories a (Cervoni et al, 1983;Kamitani et al, 1984). In the light of the present observations, however, these reports may not be contradictory.…”

“…Therefore, the electrophysiological effects of AGEPC might stem from non-specific amphiphile-membrane interaction rather than from activation of specific Paf receptors. It has been also reported that high concentrations (10-'-3 x 10-4 M) ofAGEPC were needed to induce mechanical responses in isolated vascular 40 mV preparations (Cervoni et al, 1983;Kamitani et al, 1984;Vanhoutte & Houston, 1985). Vanhoutte & Houston (1985) have suggested that the Paf-induced | 20 mg relaxation of the isolated coronary artery of the dog is not receptor-mediated, since the mechanical response was not blocked by a Paf-antagonist.…”