Relaxant effects of antidepressants on human isolated mesenteric arteries

Abstract

AimsThe therapeutic action of tricyclic agents may be accompanied by unwanted effects on the cardiovascular system. The evidence for the effects on vascular and nonvascular smooth muscle comes from animal studies. Whether these studies can be extrapolated to human vessels remains to be determined. Therefore, the present study was designed to investigate the influence of amitriptyline, nortriptyline and sertraline on the contractile responses of human isolated mesenteric arteries to electrical field stimulation, noradrenaline and potassium chloride. Methods Arterial segments (lumen diameter 0.8-1.2 mm) were obtained from portions of the human omentum during the course of 41 abdominal operations (22 men and 19 women), and rings 3 mm long were mounted in organ baths for isometric recording of tension. In some artery rings the endothelium was removed mechanically. Results In precontracted artery rings amitriptyline, nortriptyline and sertraline (3×10 −7 -10m) produced concentration-dependent relaxation that was independent of the presence or absence of vascular endothelium. Incubation with indomethacin (3×10 −6 m) reduced the pD 2 values thus indicating the participation of dilating prostanoid substances in this response. Amitriptyline and nortriptyline inhibited both the neurogenic-and noradrenaline-induced contractions. In contrast, only the highest concentration of sertraline reduced the adrenergic responses. Amitriptyline, nortriptyline and sertraline inhibited contractions elicited by KCl and produced rightward shifts of the concentration-response curve to CaCl 2 following incubation in calcium-free solution. Conclusions These results indicate that amitriptyline and nortriptyline could act as adrenoceptor antagonists and direct inhibitors of smooth muscle contraction of human mesenteric arteries, whereas sertraline might principally exert its action only as direct inhibitor of smooth muscle contraction. This relaxant mechanism involves an interference with the entry of calcium.

Sertraline Causes Strong Coronary Vasodilation: Possible Relevance for Cardioprotection by Selective Serotonin Reuptake Inhibitors

“…A recent report of Ungvari et al [8] describes the finding that fluoxetine elicited dilation of rat cerebral arteries. Sertraline produced concentration-dependent relaxation of precontracted mesenteric artery rings [15]. Although previous findings in rat aortic preparations were mixed [5,7,9], our data clearly provide evidence for the vasodilatory effects of sertraline.…”

Differential effects of two types of antidepressants, amitriptyline and fluoxetine, on anorectal motility and visceral perception

“…Moreover, antidepressants do not increase nitric oxide release which is the main neurotransmitter involved in the occurrence of recto‐anal inhibitory reflex 14, 15 . Drug‐induced myogenic relaxation is more likely since both amitriptyline and fluoxetine modify smooth muscle responses in isolated tissue models 16–19 . Both drugs abolished the contractile activity of smooth muscle by inhibiting calcium channels.…”

Chronic fluoxetine treatment alters cardiovascular functions in unanesthetized rats

“…It has been documented that fluoxetine blocks entry of Ca 2+ into arteriolar smooth muscle cells, most likely by inhibiting L-type Ca 2+ channels (Pacher et al, 1999;Ungvari et al, 2000). It is interesting to note that tricyclic antidepressants also produce relaxation in vascular smooth muscle cells (Vila et al, 1999), probably by inhibiting Ca 2+ entry (Auguet et al, 1986). On the basis of these results, a smooth muscle-relaxing effect, by interfering with Ca 2+ -entry, seems to be a general characteristic of the monoamine-uptake inhibitor compounds.…”