The Day–Night Difference of Blood Pressure Is Increased in AT1A-Receptor Knockout Mice on a High-Sodium Diet

• Published in: American journal of hypertension Vol. 23; no. 5; pp. 481 - 487
• Main Authors: Chen, Daian, Greca, Luisa La, Head, Geoffrey A., Walther, Thomas, Mayorov, Dmitry N.
• Format: Journal Article
• Language: English
• Published: Basingstoke Oxford University Press 01.05.2010; Nature Publishing Group
• Subjects: angiotensin II; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; blood pressure; Cardiology. Vascular system; circadian; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; hypertension; knockout mouse; Medical sciences; blood pressure; circadian; hypertension; angiotensin II; knockout mouse; Hypertension; Night; Peptide hormone; Rodentia; Cardiovascular disease; Octapeptide; Vertebrata; Mammalia; Sodium; Mouse; Animal; Arterial pressure; Blood pressure; Angiotensin II
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1038/ajh.2010.12

Background Abnormal circadian variation of blood pressure (BP) increases cardiovascular risk. In this study, we examined the influence of angiotensin AT1A 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 AT1A-receptor knockout mice (AT1A−/−) and their wild-type controls (AT1A+/+) placed on a normal-salt diet (NSD) or high-salt diet (HSD, 3.1% Na). Results The 24-h BP was lower in AT1A−/− than AT1A+/+ mice on a NSD (92 ± 2 and 118 ± 2mmHg, respectively), whereas the day–night BP difference (ΔDNBP) was similar between groups (11 ± 2 and 12 ± 1mmHg, respectively). HSD increased BP by 20 ± 2mmHg and ΔDNBP by 7 ± 1mmHg in AT1A−/− mice, without affecting these parameters much in AT1A+/+ mice. The ΔDNBP increase in AT1A−/− 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 AT1A−/− 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 α1-adrenergic blockade decreased BP in both strains; HSD did not affect this response in AT1A−/−, but abolished it in AT1A+/+ mice. Conclusions AT1A-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.