Animal models of hypertension: The status of nitric oxide and oxidative stress and the role of the renal medulla

Hypertension significantly contributes to overall morbidity and mortality worldwide, and animal models of hypertension provide important tools to verify the physiological and molecular mechanisms underlying the development of the disease. A review of the most important models available would provide an insight into the appropriate targets to be addressed in the treatment of different forms of human hypertension. In the animal models discussed a special attention is given to the status and pathophysiological role of nitric oxide and its interaction with reactive oxygen species and oxidative stress. Another focus of the review are the processes running in the renal medulla which are still insufficiently explored. Deficient nitric oxide synthesis and its reduced bioavailability are important determinants of hypertension since NO is recognized as a major control factor of vascular tone homeostasis. For decades perfusion of the renal medulla has also been regarded as one of the blood pressure control factors and, noteworthily, the renal medulla belongs to the tissues with the highest NO content. The list of most often applied animal hypertension models reviewed here includes variants of salt-induced hypertension, the models with genetic background: such as spontaneously hypertensive rats (SHR) and Dahl salt sensitive (SS/SR) rats, Goldblatt 2K–1C hypertensive rats, and also the pharmacologically-plus-dietary salt-induced model known as DOCA-salt hypertension.