The effect of blockade of the renin‑angiotensin‑aldosterone system on skin microcirculation in rats with impaired renal function

The renin-angiotensin-aldosterone system (RAAS) is involved in the regulation of kidney function and blood pressure (BP). In renal dysfunction, hyperactivation of the RAAS leads to an increase in BP and impaired permeability of the nephron glomerular filter. Blockade of the RAAS is one of the methods of nephroprotection. Objective. To compare the effect of an angiotensin-converting enzyme inhibitor (IACE), angiotensin I receptor blocker (ARB), and a selective slow calcium channel blocker (BCC) on the functional state of the microvasculature of the skin of rats with nephrectomy (NE), fed with a high-salt diet (HS). Design and methods. Five groups of Wistar rats were studied. The SO group: sham-operated animals that received a standard diet; the HS+NE group: rats with ¾ NE and HS (4 % NaCl); HS+NE+Ler-, HS+NE+Lis-, HS+NE+Los-groups: rats with ¾ NE and HS, that were treated with the BCC lerkanidipin (Ler, 3 mg/kg), IACE lisinopril (Lis, 30 mg/kg) or the ARB losartan (Los, 10 mg/kg), respectively. After 4 months, a study was performed using laser Doppler flowmetry (LDF). Results. In rats of the HS+NE group, uremia is accompanied by an increase in BP (by 16,9 % compared to the SO group). The treatment with IACE and ARB in rats with NE and HS prevents the rise in BP, while BCC does not reduce BP. The LDF-study showed that the increased intensity of initial skin perfusion in rats of the HS+NE group (7,2 ± 0,3 compared to 6,5 ± 0,2 p. u. in the SO group) is not corrected by BCC (6,9 ± 0,3 p. u.), but is reduced by the use of IACE (6,4 ± 0,2 p. u.) and ARB (6,1 ± 0,2 p. u.). Wavelet analysis showed that the increase in tonic effects on blood vessels in the endothelial, neurogenic and myogenic regulatory circuits, characteristic of renal dysfunction, decreases with the use of all studied drugs. RAAS blockade in rats with ¾ NE and HS does not prevent a decrease in the reactivity of skin microvessels to acetylcholine (ACh), and the use of BCC restores the response of skin blood flow to ACh to the control level. Conclusions. In Wistar rats, NE in combination with HS leads to an increase in BP, an increase in tonic effects on skin microvessels in the endothelial, neurogenic and myogenic ranges, as well as a decrease in the reactivity of skin blood flow to ACh. Inhibition of the RAAS by the treatment of IACE and ARB prevents the increase in BP, but does not improve the reactivity of skin microvessels. The use of BCC in rats with NE and HS does not reduce BP, but improves the reactivity of skin microvasculature to ACh.

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