RNO3 QTL Regulates Vascular Structure and Arterial Stiffness in the Spontaneously Hypertensive Rat

Increased arterial stiffness is an independent risk factor for hypertension, stroke, and cardiovascular morbidity. Thus, understanding the factors contributing to vascular stiffness is of critical importance. Here, we utilized a rat model containing a known quantitative trait loci (QTL) on chromosome 3 (RNO3) for vasoreactivity to assess potential genetic elements contributing to blood pressure, arterial stiffness and their downstream effects on cardiac structure and function. While no differences were found in blood pressure at any time point between parental Spontaneously Hypertensive Rats (SHR) and congenic SHR.BN3 rats, the SHR showed a significant increase in arterial stiffness measured by pulse wave velocity. The degree of arterial stiffness increased with age in the SHR and was associated with compensatory cardiac changes at 16 weeks of age, and decompensatory changes at 32 weeks, with no change in cardiac structure or function in the SHR.BN3 hearts at these time points. To evaluate the arterial wall structure, we utilized multiphoton microscopy to quantify cells and collagen content within the adventitia and media of SHR and SHR.BN3 arteries. No difference in cell numbers or proliferation rates were found, although phenotypic diversity was characterized in vascular smooth muscle cells. Herein, significant anatomical and physiological differences related to arterial structure and cardiovascular tone including, collagen, PWV, LV geometry and function, and VSMC contractile apparatus proteins were associated with the RNO3 QTL, thus providing a novel platform for studying arterial stiffness. Future studies delimiting the RNO3 QTL could aid in identifying genetic elements responsible for arterial structure and function.