Central losartan blocks natriuretic, vasopressin, and pressor responses to central hypertonic NaCl in sheep.
This study investigated the effect of intracerebroventricular administration of the angiotensin AT1 receptor antagonist losartan on the natriuresis, pressor effect, and arginine vasopressin (AVP) secretion caused by intracerebroventricular infusion of either ANG II, hypertonic saline, or carbachol. Losartan (1 mg/h) or artificial cerebrospinal fluid (CSF) was infused into the lateral ventricle before, during, and after infusions of either ANG II at 10 microg/h for 1 h, 0.75 mol/l NaCl at 50 microl/min for 20 min, or carbachol at 1.66 microg/min for 15 min. Intracerebroventricular infusions of ANG II, 0.75 mol/l NaCl, or carbachol caused increases in renal Na+ and K+ excretion, arterial pressure, and plasma AVP levels. Increases in arterial pressure, Na+ excretion, and plasma AVP concentration ([AVP]) in response to intracerebroventricular ANG II or intracerebroventricular 0.75 mol/l NaCl were either abolished or attenuated by intracerebroventricular infusion of losartan but not by intracerebroventricular infusion of artificial CSF or intravenous losartan. Intracerebroventricular losartan did not reduce the increase in plasma [AVP] or arterial pressure in response to intracerebroventricular carbachol, but it did attenuate the natriuretic response to intracerebroventricular carbachol. We conclude that an intracerebroventricular dose of losartan (1 mg/h) that inhibits responses to intracerebroventricular ANG II also inhibits vasopressin secretion, natriuresis, and the pressor response to intracerebroventricular hypertonic saline. These results suggest that common neural pathways are involved in the responses induced by intracerebroventricular administration of ANG II and intracerebroventricular hypertonic NaCl. We propose that intracerebroventricular infusion of hypertonic saline activates angiotensinergic pathways in the central nervous system subserving the regulation of fluid and electrolyte balance and arterial pressure in sheep.
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia 3052.
M L
ML
Mathai
M D
MD
Evered
M J
MJ
McKinley
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001127:Arginine Vasopressin / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000652:urine; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep; D012964:Sodium / Q000652:urine; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012462:Saline Solution, Hypertonic; D000804:Angiotensin II; D001127:Arginine Vasopressin; D002217:Carbachol; D012964:Sodium; D019808:Losartan; D011188:Potassium