Central choline suppresses plasma renin response to graded haemorrhage in rats

Abstract

1. Central administration of choline increases blood pressure in normotensive and hypotensive states by increasing plasma concentrations of vasopressin and catecholamines. We hypothesized that choline could also modulate the renin-angiotensin pathway, the third main pressor system in the body.

2. Plasma renin activity (PRA), which serves as an index of the function of the peripheral renin-angiotensin system, was determined in rats subjected to graded haemorrhage following central choline administration.

3. Intracerebroventricular (i.c.v.) injection of choline (12.5-150 mu g), a precursor of the neurotransmitter acetylcholine (ACh), inhibited the increase in PRA in rats subjected to graded haemorrhage by sequential removal of 0.55 mL blood/100 g bodyweight. Choline, in the range 50-150 mu g, increased blood pressure.

4. Intraperitoneal (i.p.) administration of 150 mu g choline failed to alter blood pressure and plasma renin responses to graded haemorrhage. Administration of a higher dose (90 mg/kg, i.p.) of choline decreased blood pressure and enhanced PRA in the first two blood samples obtained during the graded haemorrhage. Physostigmine (10 mu g, i.c.v.), ACh (10 mu g, i.c.v.), carbamylcholine (10 mu g, i.c.v.) and cytidine 5'-diphosphocholine (CDP-choline; 250 mu g, i.c.v.) increased blood pressure and attenuated plasma renin responses to graded haemorrhage.

5. Inhibition of PRA by i.c.v. choline was abolished by i.c.v. pretreatment with mecamylamine (50 mu g), but not atropine (10 mu g). Blood pressure responses to choline (150 mu g) were attenuated by pretreatment with both mecamylamine and atropine.

6. Inhibition of PRA in response to central choline administration was associated with enhanced plasma vasopressin and catecholamine responses to graded haemorrhage. Pretreatment of rats with a vasopressin antagonist reversed central choline-induced inhibition of plasma renin responses to graded haemorrhage without altering the blood pressure response.

7. In conclusion, central administration of choline inhibits the plasma renin response to graded haemorrhage. Nicotinic receptor activation and an increase in plasma vasopressin appear to be involved in this effect.