Kidney function and hypertension
Arterial hypertension is one of the most important health problems in the Western world and an important risk factor for cardio-vascular disease (CVD) and stroke. Unfortunately, these risk factors are only partly reduced during treatment with the existing drugs. Patients with treatment for their hypertension have a reduced risk for stroke of about 50 % but still a 5 times higher risk than those without hypertension. The risk for CVD is only reduced 15 % with treatment and there is a 6-7 times higher risk for CVD compared to individuals without increase in blood pressure. Therefore it is important to further investigate how hypertension develops and find new and effective principles for how to prevent and treat the disease.
Reduction of renal oxidative stress may increase nitric oxide (NO) bioavailability and thereby play an important role in preventing and/or treating CVD.
To investigate the potential roles of oxidative stress and NO-deficiency in the development of CVD. Treatment modalities that reduce oxidative stress and/or increase NO-bioavailability will be assessed in both experimental models and clinical trials in order to find new and more efficient ways to treat or prevent CVD.
We have advanced equipment for investigating renal and cardiovascular function, and imaging systems for measuring oxidative stress and NO production (in vivo and in vitro). In collaborations with physicians at different hospitals we have clinical trials to investigate the potential role of oxidative stress and NO-deficiency in CVD. In our experimental and clinical studies we aim to further investigate the link between renal and cardiovascular dysfunction, and to explore the potential benefits from reducing oxidative stress (e.g. antioxidant, nitroxide, low-sodium treatment) or increasing NO production (e.g. L-arginine or nitrate supplementation). The juxtaglomerular apparatus as shown in Fig 1 is a critical regulator of glomerular filtration rate, fluid excretion and renin relase, factors that determine blood pressure.
We believe that treatment strategies aiming to reduce oxidative stress and/or increase NO-bioavailability could be of great value in the future to treat hypertension to prevent stroke and cardio-vascular disease.
Nitric Oxide and Development of Hypertension
For the fluid balance and blood pressure level in the body, the renal control of fluid excretion rate is essential. One factor of great importance in regulation of fluid excretion is the tubuloglomerular feedback (TGF) control mechanism. In the macula densa cells, located in the distal part of the nephron, the fluid flow rate is sensed. This information is used to activate the extraglomerular mesangial cells that modulate the response via influences from both hormones and fluid volume balance factors. Activation of the TGF mechanism finally leads to a contraction of the afferent arteriole. Renal renin release is controlled via the same mechanism.
Our group studies how hormones and other factors, e.g. nerves and NO, influence the overall function of the TGF mechanism and renin release using micropuncture techniques. We also employ isolated perfused tubule and arteriole techniques using fluorophores and digital imaging methods to determine calcium, chloride and NO in the macula densa cells and in the arteriolar smooth muscle cells. NO is also measured via microelectrodes. These techniques are used to investigate the sensing step in the TGF, the modulation step in the mesangial cells and the calcium release and contractile response of the arterioles. The juxtamedullary nephron preparation is used to visualise afferent arteriolar endothelial cells to measure calcium and NO. The results of our studies aims at understanding how the TGF mechanism and renin release operates, the effect of renal oxidative stress, NO and nerves on kidney function and to find the mechanism responsible for development of arterial hypertension.
For further information about this research group please contact Professor Erik Persson: Erik.Persson@mcb.uu.se