Age-dependent changes in the mechanisms of endothelial-dependent dilatation of pial arterial vessels in SHR rats

Authors

DOI:

https://doi.org/10.33910/2687-1270-2021-2-2-181-188

Keywords:

NO, calcium-activated high-conductance potassium channels, hypertension, aging, pial vessels

Abstract

The study investigated the role of age-related changes in the contribution of NO and IKCa-channels to acetylcholine-induced dilation of pial arteries in spontaneously hypertensive rats (SHR). We used intravital microphotography (×470) to evaluate the responses of pial arteries to acetylcholine chloride (ACh, 10−7 M, 5 min) with and without blockade of NO (L-NAME, 10−3 M) and IKCa-channels (klotrimazole,10−5 M) in SHR rats aged 4 and 18 months. The number and degree of vascular dilatation was measured from the erythrocyte flow width in three individual groups of arteries: small (less than 20 μm in diameter), medium (20–40 μm) and large (more than 40 μm). It was found that in young SHR rats, NO plays a significant role in the ACh-mediated dilation of small and large-diameter vessels. The role of IKCa-channels in endothelium-dependent dilatation mainly manifests itself in the group of small vessels and decreases with an increase in artery diameter. Aging, accompanied by hypertension, reduces the role of IKCa-channels and increases the contribution of NO to the dilatation of pial arterial vessels of all sizes.

References

ЛИТЕРАТУРА

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Ahn, S. J. Fancher, I. S., Bian, J.-T. et al. (2017) Inwardly rectifying K+ channels are major contributors to flow-induced vasodilatation in resistance arteries. The Journal of Physiology, vol. 595, no. 7, pp. 2339–2364. https://www.doi.org/10.1113/JP273255

Bernatova, I. (2014) Endothelial dysfunction in experimental models of arterial hypertension: Cause or consequence? BioMed Research International, vol. 2014, article 598271. http://dx.doi.org/10.1155/2014/598271

De Silva, T. M., Modrick, M. L., Dabertrand, F., Faraci, F. M. (2018) Changes in cerebral arteries and parenchymal arterioles with aging: Role of Rho kinase 2 and impact of genetic background. Hypertension, vol. 71, no. 5, pp. 921–927. https://www.doi.org/10.1161/HYPERTENSIONAHA.118.10865

Diaz-Otero, J. M., Yen, T.-C., Fisher, C. et al. (2018) Mineralocorticoid receptor antagonism improves parenchymal arteriole dilation via a TRPV4-dependent mechanism and prevents cognitive dysfunction in hypertension. American Journal of Physiology — Heart and Circulatory Physiology, vol. 315, no. 5, pp. H1304–H1315. https://www.doi.org/10.1152/ajpheart.00207.2018

Gorshkova, O. P., Shuvaeva, V. N. (2020) Age-related changes in the role of calcium-activated potassium channels in acetylcholine mediated dilatation of pial arterial vessels in rats. Journal of Evolutionary Biochemistry and Physiology, vol. 56, no. 2, pp. 145–152. https://doi.org/10.1134/S0022093020020064

Goto, K., Ohtsubo, T., Kitazono, T. (2018) Endothelium-dependent hyperpolarization (EDH) in hypertension: The role of endothelial ion channels. International Journal of Molecular Sciences, vol. 19, no. 1, article 315. https://www.doi.org/10.3390/ijms19010315

Levina, V. I., Trukhacheva, L. A., Pyatakova, N. V. et al. (2004) Investigation of the NO-donor activity of the antimicrobial drug tinidazole. Pharmaceutical Chemistry Journal, vol. 38, no. 1, pp. 15–18. https://www.doi.org/10.1023/B:PHAC.0000027637.23022.e9

Pires, P. W., Dams Ramos, C. M., Matin, N., Dorrance, A. M. (2013) The effects of hypertension on the cerebral circulation. American Journal of Physiology — Heart and Circulatory Physiology, vol. 304, no. 12, pp. H1598– H1614. https://www.doi.org/10.1152/ajpheart.00490.2012

Taddei, S., Virdis, A., Mattei, P. et al. (1995) Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation, vol. 91, pp. 1981–1987. https://www.doi.org/10.1161/01.cir.91.7.1981

Wilson, C., Zhang, X., Buckley, C. et al. (2019) Increased vascular contractility in hypertension results from impaired endothelial calcium signaling. Hypertension, vol. 74, no. 5, pp. 1200–1214. https://www.doi.org/10.1161/ HYPERTENSIONAHA.119.13791

REFERENCES

Ahn, S. J. Fancher, I. S., Bian, J.-T. et al. (2017) Inwardly rectifying K+ channels are major contributors to flow-induced vasodilatation in resistance arteries. The Journal of Physiology, vol. 595, no. 7, pp. 2339–2364. https://www.doi.org/10.1113/JP273255 (In English)

Bernatova, I. (2014) Endothelial dysfunction in experimental models of arterial hypertension: Cause or consequence? BioMed Research International, vol. 2014, article 598271. http://dx.doi.org/10.1155/2014/598271 (In English)

Chertok, V. M., Kotsyuba, A. E. (2011) Izmenenie indutsibel’noj NO-sintazy v pial’nykh arteriyakh raznogo diametra u gipertezivnykh krys [Changes in inducible NO-synthase in pial arteries of different diameters in hypertensive rats]. Bulleten’ eksperimental’noj biologii i meditsiny — Bulletin of Experimental Biology and Medicine, vol. 152, no. 8, pp. 220–223. (In Russian)

De Silva, T. M., Modrick, M. L., Dabertrand, F., Faraci, F. M. (2018) Changes in cerebral arteries and parenchymal arterioles with aging: Role of Rho kinase 2 and impact of genetic background. Hypertension, vol. 71, no. 5, pp. 921–927. https://www.doi.org/10.1161/HYPERTENSIONAHA.118.10865 (In English)

Diaz-Otero, J. M., Yen, T.-C., Fisher, C. et al. (2018) Mineralocorticoid receptor antagonism improves parenchymal arteriole dilation via a TRPV4-dependent mechanism and prevents cognitive dysfunction in hypertension. American Journal of Physiology — Heart and Circulatory Physiology, vol. 315, no. 5, pp. H1304–H1315. https://www.doi.org/10.1152/ajpheart.00207.2018 (In English)

Gorshkova, O. P., Shuvaeva, V. N. (2020) Age-related changes in the role of calcium-activated potassium channels in acetylcholine mediated dilatation of pial arterial vessels in rats. Journal of Evolutionary Biochemistry and Physiology, vol. 56, no. 2, pp. 145–152. https://doi.org/10.1134/S0022093020020064 (In English)

Goto, K., Ohtsubo, T., Kitazono, T. (2018) Endothelium-dependent hyperpolarization (EDH) in hypertension: The role of endothelial ion channels. International Journal of Molecular Sciences, vol. 19, no. 1, article 315. https://www.doi.org/10.3390/ijms19010315 (In English)

Levina, V. I., Trukhacheva, L. A., Pyatakova, N. V. et al. (2004) Investigation of the NO-donor activity of the antimicrobial drug tinidazole. Pharmaceutical Chemistry Journal, vol. 38, no. 1, pp. 15–18. https://www.doi.org/10.1023/B:PHAC.0000027637.23022.e9 (In English)

Pires, P. W., Dams Ramos, C. M., Matin, N., Dorrance, A. M. (2013) The effects of hypertension on the cerebral circulation. American Journal of Physiology — Heart and Circulatory Physiology, vol. 304, no. 12, pp. H1598–H1614. https://www.doi.org/10.1152/ajpheart.00490.2012 (In English)

Taddei, S., Virdis, A., Mattei, P. et al. (1995) Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation, vol. 91, pp. 1981–1987. https://www.doi.org/10.1161/01.cir.91.7.1981 (In English)

Wilson, C., Zhang, X., Buckley, C. et al. (2019) Increased vascular contractility in hypertension results from impaired endothelial calcium signaling. Hypertension, vol. 74, no. 5, pp. 1200–1214. https://www.doi.org/10.1161/ HYPERTENSIONAHA.119.13791 (In English)

Published

2021-06-28

Issue

Section

Experimental articles