In an experimental model of
hemorrhagic shock resulting in the death of almost all rats within 20-30 min, centrally active
cholinomimetic drugs are reported to induce a prompt, sustained and dose-dependent improvement in blood pressure and survival rate claimed to be due to nicotinic, but not
muscarinic actions. In the present study,
cholinergic receptor agonist,
oxotremorine (50 micrograms/kg, i.v.) increased mean arterial pressure (from 22 +/- 1 to 123 +/- 3 mm Hg) and 60 min-survival rate (from 0% to 92%) in rats bled to
hypovolemic shock.
Atropine (2 mg/kg, i.v.) pretreatment inhibited the pressor effect of
oxotremorine significantly, but did not modify its effect on survival rate. On the other hand, pretreatment with
mecamylamine (50 micrograms, i.c.v.) almost abolished the reduction in mortality rate, but inhibited the pressor effect of
oxotremorine, partially. These results indicate that
oxotremorine-induced pressor response and decrease in mortality in rats with severe
hemorrhagic shock are primarily mediated via central
muscarinic and
nicotinic receptors, respectively. AV3V region was previously reported to be involved in pressor and
natriuretic effects of i.c.v.
carbachol in normotensive rats. In the present study, the electrolytic lesions of AV3V region significantly inhibited
oxotremorine-induced increases in both blood pressure and survival rate in rats subjected to
hemorrhagic shock. These findings indicate that AV3V region plays a major role in
cholinergic cardiovascular control in hypotensive animals as well as normotensives.