[Blood pressure variability-induced aggravation of hypertensive organ damages].

There is increasing evidence that not only the elevation of systolic and diastolic blood pressure(BP) but also the increase in BP variability (or fluctuation) are associated with hypertensive organ damages and the morbidity and mortality of cerebrovascular and cardiovascular events, as well as cognitive dysfunction. However, the molecular mechanism whereby the increase in BP variability aggravates hypertensive organ damages remains unknown. Thus, we created a rat chronic model of a combination of hypertension and large BP variability by performing bilateral sino-aortic denervation in spontaneously hypertensive rat. A series of our studies using this model revealed that large BP variability induces chronic myocardial inflammation by activating local angiotensin II and mineralocorticoid receptor systems and thereby aggravates cardiac hypertrophy and myocardial fibrosis, leading to systolic dysfunction, in hypertensive hearts. In addition, large BP variability induces the aggravation of arteriolosclerotic changes and ischemic cortical fibrosis in hypertensive kidney via local angiotensin II system. It is interesting that the initial target sites of the large BP variability are the intramyocardial arterioles in the heart and pre-glomerular arterioles in the juxtamedullary renal cortex, so called "strain vessels". Accordingly, we advocate new concept that the large BP-induced aggravation of hypertensive organ damage is attributable to "strain vessel vasculopathy".