NaCl injections in brain induce natriuresis and blood pressure responses sensitive to ANG II AT1 receptors.
In the present study we tested the hypothesis that the natriuretic and pressor effects of intracerebroventricularly (icv) injected hypertonic saline involve a central angiotensinergic pathway. All experiments were performed in conscious Wistar rats. Bolus injections of hypertonic saline (0.19, 0.23, 0.30, and 0.60 M icv; injection volume 5 microliters) induced a concentration-dependent increase of renal sodium excretion without affecting urinary flow. The increase in renal sodium excretion after the two highest saline concentrations was accompanied by significant increases in mean arterial blood pressure (MAP). Pretreatment with the angiotensin (ANG) AT1 receptor antagonist, losartan (5 micrograms icv), reduced the natriuretic effect of 0.23 and 0.30 M saline but did not affect the natriuresis induced by 0.60 M saline. The increase in MAP after 0.30 and 0.60 M saline icv was markedly attenuated by intracerebroventricular pretreatment with losartan. Our results demonstrate the involvement of a central angiotensinergic mechanism in the natriuretic and pressor responses to hypertonic saline. In addition to the ANG II-mediated natriuresis, an additional natriuretic mechanism, independent of ANG II and associated with the saline-induced pressor effect, seems to be recruited with increasing concentrations of saline in the cerebrospinal fluid.
Rohmeiss
P
P
Department of Pharmacology, University of Kiel, Germany.
Beyer
C
C
Nagy
E
E
Tschöpe
C
C
Höhle
S
S
Strauch
M
M
Unger
T
T
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D007267:Injections; D019808:Losartan; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D012462:Saline Solution, Hypertonic; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D012965:Sodium Chloride; D019808:Losartan