Rats are Protected from the Stress of Chronic Pressure Overload Compared with Mice

Abstract

Little is known about differences in responses to cardiac stress in different rodent species, i.e., rats vs mice. The goal of this investigation was to compare the effects of chronic, 1‐month, thoracic aortic constriction (TAC) in Sprague Dawley rats and C57BL/6 mice. Sham and TAC procedures were conducted in both rodent groups. TAC, in the thoracic aorta, just distal to the aortic valve, induced similar left ventricular (LV) aortic pressure gradients across the aortic constriction, but there was no pressure gradient in sham operated animals. LV ejection fraction was no different in sham rats and mice (73 ± 1%), and did not fall with TAC in the rats, but fell significantly, p<0.05, in mice with TAC to 59 ± 2%. LV end diastolic pressure was also not different in sham rats and mice (5 ± 1 mmHg) and did not increase with TAC in rats, but increased, p<0.05, in TAC mice to 15 ± 2 mmHg. The next goal was to examine potential mechanisms mediating these major differences in LV function. First, we examined LV systolic wall stress, which was also similar in sham rats and mice (73 ± 1 kdyn/cm2) and did not rise significantly in TAC rats, but rose, p<0.05, to 117 ± 7kdyn/cm2 in TAC mice. Since TAC induces LV hypertrophy, which in turn, impairs subendocardial coronary perfusion and coronary reserve, and consequently LV function, angiogenesis and arteriogenesis were examined next, as these mechanisms could alleviate the coronary subendocardial hypoperfusion. Immunofluorescent Ki67 staining of capillaries and arterioles revealed increased angiogenesis, i.e., greater increases, p<0.05, in capillaries in TAC rats (6.7 ± 0.3 Ki67+Isolectin positive cells/field) than in TAC mice (4.2 ± 1.1 Ki67+Isolectin positive cells/field). Arteriogenesis was also increased more in TAC rats than TAC mice, reflected by greater increases, p<0.05, in Ki67 stained arterioles in TAC rats (19.8 ± 0.3 Ki67+SMCα positive cells/field) vs TAC mice (7.9 ± 1.2 Ki67+SMCα positive cells/field). Thus, rats are more resistant to development of cardiac failure with chronic TAC compared with mice. The mechanism of this protection involved reduced LV systolic wall stress and increased angiogenesis and arteriogenesis in the rats with chronic pressure overload.Support or Funding InformationFunding support: NIH R01 HL124282This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.