Objective: We determined whether chronic reductions in carotid blood flow elicit salt-sensitive hypertension through regulation of the brain renin-angiotensin system (RAS).
Design and methods: Both internal carotid arteries of male Wistar rats were ligated over a 1-week period. Carotid-ligated or sham-operated rats were treated with a high-salt (8% NaCl diet and 1% NaCl drinking water) or low-salt (0.3% NaCl diet and distilled water) diet for 6 weeks. At the end of the experiment, expression of the RAS mRNAs in the brain was measured. Effects of a 6-day intracerebroventricular infusion of CV-11974, a selective non-peptide angiotensin II type 1 (AT1) receptor blocker, were investigated in carotid-ligated rats administered high-salt diet.
Results: High-salt administration increased systolic arterial pressure compared with low-salt administration in sham-operated rats [168 +/- 4 mmHg (n = 10) versus 149 +/- 3 mmHg (n = 10), P < 0.001] and in carotid-ligated rats [202 +/- 5 mmHg (n = 10) versus 153 +/- 2 mmHg (n = 10), P < 0.0001]. Systolic arterial pressure, urinary excretion of vasopressin and norepinephrine, and expression of renin, angiotensin I converting enzyme, and AT1 receptor mRNAs in the hypothalamus were greater in carotid-ligated rats than in sham-operated rats treated with high salt. In contrast, these parameters did not differ between carotid-ligated and sham-operated rats treated with low salt. Intracerebroventricular infusion of CV-11974 abolished the increase in these parameters in carotid-ligated rats treated with the high-salt diet.
Conclusions: Chronic reductions in carotid blood flow may cause salt-sensitive hypertension in normotensive rats by activating the hypothalamic RAS.