Sebastian Garcia

Introduction: Essential hypertension involves an elevated systolic or diastolic blood pressure, usually greater than  mmHg, that is not caused by secondary factors such as underlying disease^1,4. Angiotensin II plays a major role in the development of essential hypertension by increasing the fluid volume in the blood due to salt reuptake by the kidneys^2,5. Overtime, the vascular smooth muscle cells can change in response to angiotensin II-induced NOX1 expression, which promotes oxidative stress through the creation of reactive oxygen species. This can lead to inflammation and chronic hypertension^2,5. Studies have shown that reactive oxygen species can hyperoxidize proteins which can lead to endoplasmic reticulum stress, and cellular senescence^6,8. In addition, reactive oxygen species can suppress T-type Ca²⁺ channels, and cause early and late inflammatory responses ^7,9. Further insight into T-type Ca²⁺ suppression as well as early and late inflammatory response may help in understanding the role of NOX1 in essential hypertension. Methods: Human umbilical vein endothelial cells (HUVECs) and cerebral arterial smooth muscle cells were utilized. HUVECs were treated with angiotensin II and western blot was used to determine NOX1 protein and inflammatory protein (IL-6, MCP-1, TNF-a) concentrations at different time intervals. Cerebral arterial smooth muscle cells were treated with angiotensin II and NOX1 inhibitors (apocynin & ML-171), followed by the measurement of current density flowing through T-type Ca²⁺ channels using a patch-clamp amplifier. Results: Angiotensin II-induced NOX1 expression caused a peak increase in inflammatory proteins at 4 hours in HUVECs, which was associated with the peak increase of NOX1 protein levels. In cerebral arterial smooth muscle cells, angiotensin II caused a decrease in current flow through T-type Ca²⁺ channels; however, the current flow returned to normal after the administration of NOX1 inhibitors. Discussion: These findings show that NOX1 levels fluctuate throughout the day and cause high levels of inflammation at different time intervals⁹. In addition, NOX1 proteins decrease the flow of current in T-type Ca²⁺ channels⁷. The decrease in current prevents hyperpolarization of cerebral arterial smooth muscle cells by decreasing BK_Ca activity⁷. Although L-type Ca²⁺ channels are primarily involved in vasoconstriction, T-type Ca²⁺ channels help modulate disproportionate narrowing of blood vessels through BK_Ca activity, which causes hyperpolarization of smooth muscle and vessel relaxation⁷. Angiotensin II-induced NOX1 expression can cause oxidative stress which may lead to essential hypertension through excess vasoconstriction and inflammation.

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