Effects of central losartan on plasma renin and centrally mediated natriuresis

Abstract

Because intracerebroventricular (ICV) infusion of hypertonic saline or angiotensin II (Ang II) both induce water drinking, vasopressin secretion, natriuresis and increased arterial pressure, the possibility that common neural pathways mediate responses to ICV Ang II and hypertonic saline has been investigated. This was done by testing the effect of ICV infusion of the Ang II antagonist losartan on the natriuretic and pressor responses to ICV hypertonic NaCl in sheep. The effect of ICV losartan on plasma renin concentration (PRC) was also investigated. Infusion of losartan (1 mg/hr) into a lateral ventricle prevented both natriuretic and pressor responses to infusion of 0.6 mol/liter NaCl into a lateral ventricle at 1 ml/hr. In another experiment, ICV losartan at 1 mg/hr caused a pronounced increase in the PRC of Na-depleted sheep, while ICV Ang II at 3 micrograms/hr decreased PRC. The results suggest that: (i) a central angiotensinergic pathway may mediate osmoregulatory responses to centrally administered hypertonic saline, and (ii) a central angiotensinergic pathway may have a tonic inhibitory influence on renin secretion in Na-depleted animals.

Review: AT1-receptors in the central nervous system

“…118 Prior ICV treatment with losartan blocks this response and, in fact, central losartan treatment further increases plasma renin levels in sodium-depleted sheep, 118 indicating AT 1 -receptor involvement. Central administration of Ang II to the lateral ventricle also causes a reduction in renal sympathetic nerve activity, 81 which may be a factor contributing to the reduction in plasma renin levels with this treatment.…”

Neural Mechanisms Subserving Central Angiotensinergic Influences on Plasma Renin in Sheep

“…ICV infusion of the angiotensin AT 1 receptor antagonist losartan elevates PRC in sodium-depleted sheep, suggesting that an angiotensinergic pathway in the brain may exert a tonic inhibitory influence on renin secretion in these animals. 8 We have observed that ICV infusion of either Ang II or hypertonic saline suppresses PRC in sodium-depleted sheep without increasing arterial pressure. 8,9 This contrasts with the pressor effects of such ICV infusions in sodium-replete sheep, 6 suggesting that the reduced plasma renin levels are not a reflex response to baroreceptor activation.…”

“…8 We have observed that ICV infusion of either Ang II or hypertonic saline suppresses PRC in sodium-depleted sheep without increasing arterial pressure. 8,9 This contrasts with the pressor effects of such ICV infusions in sodium-replete sheep, 6 suggesting that the reduced plasma renin levels are not a reflex response to baroreceptor activation. As well as suppressing PRC, ICV infusion of either Ang II or hypertonic NaCl reduces renal sympathetic nerve activity considerably in conscious sheep, 6 showing that the reduced PRC may have resulted from reduced renal nerve activity, a conclusion reached earlier from studies that used renal denervation.…”

“…[3][4][5][6][7][8] Whereas intracerebroventricular (ICV) infusions of Ang II or renin reduce plasma renin concentration (PRC), arterial pressure also increases. [3][4][5][6][7][8] Thus, the inhibition of renin release may be mediated by renal or arterial baroreflexes secondary to the rise in pressure. ICV infusion of the angiotensin AT 1 receptor antagonist losartan elevates PRC in sodium-depleted sheep, suggesting that an angiotensinergic pathway in the brain may exert a tonic inhibitory influence on renin secretion in these animals.…”

Medial septal area ANG II receptor subtypes in the regulation of urine and sodium excretion induced by vasopressin

“…[36][37][38] The effects of AVP on sodium excretion are less conclusive than for urinary flow. Recent studies have shown that the increase in urine excretion caused by the AVP-V2 receptor blockade is related to an increase in blood sodium concentration and plasma osmolality.…”