Neurohumoral mechanism in the natriuretic action of intracerebroventricular administration of renin.
BACKGROUND
Intracerebroventricular (i.v.t.) administration of renin (R) decreases urinary volume and increases urinary sodium excretion. We investigated whether i.v.t.-R-induced natriuresis could be associated with the release of atrial natriuretic peptide (ANP), its interaction with renal ANP-A receptors (ANPR-A) and the subsequent increase of urinary cyclic 3-5 guanosine monophosphate (cGMP).


METHODS
In i.v.t. cannulated rats, the left carotid artery was catheterised with PE-50 tubing for blood collection, renin was injected i.v.t. and arterial blood samples were collected at 0, 2, 5, 10 and 15 minutes of injection, and urinary sodium and cGMP excretion at 1-, 3- and 6-hour periods of urine collection. Plasma ANP levels and urinary cGMP were determined by radioimmunoassay, and each urine sample was analysed for sodium concentration using a flame photometer.


RESULTS
Our results demonstrate that i.v.t.-R administration increases plasma ANP levels after two minutes of injection and urinary cGMP concentration at 1-, 3- and 6 hour period of urine collection. The natriuretic action induced by i.v.t.-R was blunted by peripheral administration of anantin, an ANPR-A antagonist. We assessed the role of brain angiotensin II (Ang II) AT1-receptors on the i.v.t.-induced antidiuresis, natriuresis and cGMP urinary excretion, the last as an indirect index of ANP secretion. Blockade of brain Ang II AT1-receptors with losartan (LOS; 120 microg/3 microl, i.v.t.), inhibited the antidiuretic action and blocked the increased urinary sodium and cGMP excretion induced by i.v.t.-R (7.14 mGU/5 microl). The increase in urinary cGMP was independent of nitric oxide synthase stimulation, since L-NAME pre-treatment did not alter the renal actions induced by i.v.t.-R.


CONCLUSIONS
Our results suggest that there is a link between the brain and the kidney. The activation of brain angiotensinergic neurons and stimulation of AT1- receptors may stimulate the release of ANP to the circulation. The released ANP circulates to the kidneys where it acts through renal ANPR-As and the consequent increase in cGMP to produce natriuresis.
Zavala
Lida
L
School of Medicine, Universidad Experimental Francisco de Miranda, Coro Estado Falcon, Venezuela.
Barbella
Yarisma
Y
Israel
Anita
A
D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001921:Brain / Q000378:metabolism; D006152:Cyclic GMP / Q000652:urine; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors; D012083:Renin / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors; D000092502:Renin Inhibitors
D047228:Angiotensin II Type 1 Receptor Blockers; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D019808:Losartan; D018377:Neurotransmitter Agents; D010456:Peptides, Cyclic; D044140:Receptor, Angiotensin, Type 1; D017461:Receptors, Atrial Natriuretic Factor; D012083:Renin; D000092502:Renin Inhibitors; C068090:anantin