The day-night difference of blood pressure is increased in AT(1A)-receptor knockout mice on a high-sodium diet.
BACKGROUND
Abnormal circadian variation of blood pressure (BP) increases cardiovascular risk. In this study, we examined the influence of angiotensin AT(1A) receptors on circadian BP variation, and specifically on its behavioral activity-related and -unrelated components.


METHODS
BP and locomotor activity were recorded by radiotelemetry in AT(1A)-receptor knockout mice (AT(1A)(-/-)) and their wild-type controls (AT(1A)(+/+)) placed on a normal-salt diet (NSD) or high-salt diet (HSD, 3.1% Na).


RESULTS
The 24-h BP was lower in AT(1A)(-/-) than AT(1A)(+/+) mice on a NSD (92 +/- 2 and 118 +/- 2 mm Hg, respectively), whereas the day-night BP difference (DeltaDNBP) was similar between groups (11 +/- 2 and 12 +/- 1 mm Hg, respectively). HSD increased BP by 20 +/- 2 mm Hg and DeltaDNBP by 7 +/- 1 mm Hg in AT(1A)(-/-) mice, without affecting these parameters much in AT(1A)(+/+) mice. The DeltaDNBP increase in AT(1A)(-/-) mice was caused by nondipping BP during the inactive late-dark period. Conversely, BP rise associated with circadian behavioral activation during the early dark period was not altered by HSD in AT(1A)(-/-) mice. The BP change associated with spontaneous ultradian activity-inactivity bouts was also similar between strains on HSD as was the BP rise associated with induced (cage-switch) behavioral activity. Ganglionic or alpha(1)-adrenergic blockade decreased BP in both strains; HSD did not affect this response in AT(1A)(-/-), but abolished it in AT(1A)(+/+) mice.


CONCLUSIONS
AT(1A)-receptor deficiency, when combined with HSD, can increase circadian BP difference in mice. This increase is mediated principally by activity-unrelated factors, such as the nonsuppressibility of basal resting sympathetic tone by HSD, thus suggesting a form of salt-/volume-dependent hypertension.
Chen
Daian
D
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
La Greca
Luisa
L
Head
Geoffrey A
GA
Walther
Thomas
T
Mayorov
Dmitry N
DN
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012982:Sodium, Dietary / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D044140:Receptor, Angiotensin, Type 1; D012982:Sodium, Dietary