Altered Synthesis of Hydrogen Sulfide Plays a Key Role in the Pathogenesis of Renovascular Hypertension

Clarence Lim

Introduction. Renovascular hypertension is defined as a systolic blood pressure greater than 130 mmHg or a diastolic blood pressure greater than 80 mmHg with renovascular etiologies7. Renovascular hypertension accounts for approximately 3% of cases in unselected hypertensive patients7. Altered metabolism is a key cause in hypertension5,6,8,9. Studies have shown hydrogen sulfide (HS), an endogenous substance known as a vasodilator, mediates the hypoxic response in coronary artery of pig hearts1. Other studies show that reduction of HS upregulates the level of angiotensin II and oxidative stress enzymes while downregulating antioxidant enzymes2,3. Further studies have shown that HS play a role in epigenetics in offspring4. These findings could suggest a potential medical therapy for renovascular hypertension. Methods. Five individual experiments were conducted to analyze the relationship between HS and the changes in hypertension activity. The first experiment determined whether HS mediates the hypoxic response by contracting the coronary arteries of pig hearts through a thromboxane A2 analog1. The second experiment sought to determine the effect HS has on the level of angiotensin II by through radioimmunoassay2. The third experiment took a further step to see what other oxidative-stress and antioxidant enzymes are affected by measuring enzyme activity in 2K1C and controlled rats3. The fourth experiment determined whether HS has any protective effect on offspring via measuring methylation of the AT1B gene4. The fifth experiment determined whether taurine, a sulfur-containing amino acid, has any effect on prehypertensive patients through a double-blind, randomized, placebo-controlled trial10. Results. The first experiment showed that hypoxia produces a biphasic vasomotor response, an initial transient contraction followed by a prolonged and prominent vasorelaxation1. The second experiment showed an increase of angiotensin II in 2K1C rats2. The third experiment showed increased levels of oxidative stress enzymes in 2K1C rats and reduced levels of SOD, an antioxidant enzyme3. The fourth experiment showed increased methylation of the AT1b gene with prenatal or postnatal administration with HS4. The fifth experiment showed a reduction of blood pressure and improvement of vasodilation in prehypertensive individuals with the taurine supplementation10. Conclusions. Studies have shown that there is a correlation between levels HS and the progression of renovascular hypertension, and by introducing HS, blood pressure can be reduced. As more investigations of HS and the mechanisms of renovascular hypertension are performed, new prognostic and therapeutic approaches can be conducted.

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