Preclinical and clinical studies have shown that reduced NO generation due to compromised eNOS (primarily found in the endothelial cells of the afferent arteriole) and/or neuronal nNOS (primarily expressed in the macula densa cells) activity can increase preglomerular resistance, reduce glomerular perfusion and filtration and increase tubular reabsorption of sodium, which subsequently lead to the development or progression of HT and kidney damage [84,85]. The gene discussed is NOS1; the disease is hematocrit.