**1. Introduction**

Hypertension is the leading preventable risk factor for cerebro-cardiovascular complications, including heart failure and stroke. Effective anti-hypertensive drugs with different pharmacological actions have been developed; nevertheless, it is deemed that there are 1.28 billion hypertensive patients globally and 0.7 billion or more patients are untreated [1]. Given the resulting mortality and disability as well as the high prevalence, hypertension is still a major public health burden in the world.

It is needless to say that gene-targeted knock-out (KO) and knock-in (KI) or transgenic rodent models have greatly contributed to understanding the pathophysiological basis of hypertension and its vascular complications. In particular, mice have been widely used as the best experimental animal since the gene engineering technique to create KO models was established for over 30 years ago. By contrast, it had been technically difficult to create KO rats for a long time because of the difficulty of rat ES cell culture. Recent advances in genome-editing technologies, however, have made it possible to easily create KO rats similar to mice [2,3]. Given that spontaneous cerebro-cardiovascular disease models, such as Dahl salt-sensitive (SS) and stroke-prone spontaneously hypertensive rats (SHRSP), have been commercially available, a genome-editing strategy using the rat disease models has much potential to clarify the novel pathogenesis of hypertension. In this review, we outlined recent advances in basic research for hypertension using KO and KI or transgenic rodent models to clarify the underlying mechanisms.
