Key result
Intracerebroventricular ANP or losartan significantly decreased arterial blood pressure only in ANP knockout mice, indicating hypertension is associated with increased central AT1-receptor activation.
Why the study?
Does central AT1-receptor activation or systemic vasopressin sustain hypertension in ANP knockout mice?
Does central AT1-receptor activation or systemic vasopressin sustain hypertension in ANP knockout mice?
Permanently elevated blood pressure in ANP knockout mice is associated with increased central nervous angiotensin II AT1-receptor activation rather than increased vasopressin importance.
Does not implicate vasopressin in ANP-knockout hypertension; leaves open central AT1 mechanisms for targeted investigation.
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.
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Ackermann et al. (2000) studied Hypertension. Intracerebroventricular ANP or losartan, and intravenous V1-receptor antagonist vs. Physiological saline was evaluated on Carotid arterial blood pressure (ABP). Intracerebroventricular ANP or losartan significantly decreased arterial blood pressure only in ANP knockout mice, indicating hypertension is associated with increased central AT1-receptor activation.
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