Increased central AT(1)-receptor activation, not systemic vasopressin, sustains hypertension in ANP knockout mice.
We tested the hypothesis that hypertension in atrial natriuretic peptide (ANP) knockout mice is caused in part by disinhibition of angiotensin II-mediated vasopressin release. Inactin-anesthetized F(2) homozygous ANP gene-disrupted mice (-/-) and wild-type (+/+) littermates were surgically prepared for carotid arterial blood pressure measurement (ABP) and background intravenous injection of physiological saline or vasopressin V(1)-receptor antagonist (Manning compound, 10 ng/g body wt) and subsequent intracerebroventricular (left lateral ventricle) injection of saline (5 microl) or ANP (0.5 microg) or angiotensin II AT(1)-receptor antagonist losartan (10 microg). Only (-/-) showed significant decrease in ABP after intracerebroventricular ANP or losartan. Both showed significant hypotension after intravenous V(1) antagonist, but there was no difference between their responses. We conclude that 1) vasopressin contributes equally to ABP maintenance in ANP-disrupted mice and wild-type controls; 2) permanently elevated ABP in ANP knockouts is associated with increased central nervous angiotensin II AT(1)-receptor activation; 3) disinhibition of central nervous angiotensin II AT(1) receptors in ANP-deficient animals does not lead to a significant increase in the importance of vasopressin as a mechanism for blood pressure maintenance.
Ackermann
U
U
Department of Physiology, University of Toronto, Toronto, Ontario, Canada, M5S 1A8. u.ackermann@utoronto.ca
Azizi
N
N
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D007275:Injections, Intravenous; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D014667:Vasopressins / Q000097:blood*
D000959:Antihypertensive Agents; D006727:Hormone Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014667:Vasopressins; D000804:Angiotensin II; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D009320:Atrial Natriuretic Factor; D019808:Losartan