The hypotensive action of puffer fish toxin

Effects of Tetrodotoxin on the Mammalian Cardiovascular System

“…Their studies provided overwhelming evidence that the heart belongs to the very few organs that remain nearly unaffected, even at large sub-lethal or lethal TTX doses. Note that intoxication often required artificial ventilation, but the heart continued beating regularly [37–41,44,46,47]. Nevertheless, TTX exerts pronounced depressive effects on the circulatory system (Table 2).…”

“…A direct negative inotropic or chronotropic action of TTX in intoxicated animals was excluded also in most if not all subsequent studies. For example, Cheng and colleagues [43,46] found that the blood flow in the ascending aorta was not measurably altered when injecting a dose of 0.25 MLD into right external jugular vein (Table 2), demonstrating that the simultaneously observed arterial hypotension was caused by peripheral vasodilatation only.…”

“…Microinjection of the same TTX dose into the nucleus tractus solitarii (NTS), a well known vasodepressive and cardio-inhibitory area, caused an increase in blood pressure. Secondly, vasodilatation resulted mainly from a conduction block in sympathetic fibers [27,35,37,39,41,43,46]. Thirdly, low doses of TTX may directly affect vascular smooth muscles [39].…”

“…In some studies, even lethal doses of 7–10 μg/kg did not significantly alter heart rate in cats [38]. When heart rate reduction was measured, it often occurred subsequent to the onset of hypotension [38,40,45,46]. Severely intoxicated guinea pigs (15 μg/kg, i.p.)…”

“…At this dose, arterial blood pressure was reduced from 120–150 to 40–55 mmHg [43]. In a similar study, injection of 5 μg/kg caused a rapid fall in blood pressure at an initially unchanged heart rate and stroke volume [46]. Furthermore, slow intravenous TTX injections of 9.3 μg/kg, a lethal dose for dogs, did not alter the cardiac index until respiratory arrest [44].…”