Blood pressure in 15 inbred mouse strains and its lack of relation with obesity and insulin resistance in the progeny of an NZO/HILtJ x C3H/HeJ intercross.

We characterized the systolic and diastolic blood pressures of 10-week-old males from 15 inbred mouse strains and found that blood pressures among strains were continuously distributed and that strain C3H/HeJ had the lowest mean systolic and diastolic pressure (100.5 +/- 3.2 and 66.8 +/- 3.5 mmHg), and a strain with obesity and diabetes, NZO/HILtJ, had the highest (132.4 +/- 3.1 and 86.6 +/- 6.9 mmHg). To understand the relationship of blood pressure with insulin resistance and obesity, we produced F1 and F2 progeny from reciprocal crosses of NZO, the strain with obesity, diabetes, and high blood pressure, and the strain with the lowest blood pressures, C3H/HeJ. Mean systolic pressures of 10-week-old (NZO x C3H)F1 and (C3H x NZO)F1 males were similar to each other (114.9 +/- 3.8 and 117.2 +/- 5.0 mmHg) and were intermediate to those of the parental strains. Systolic pressure of F2 males (n = 223) was distributed normally about the mean, suggesting that blood pressure is a polygenic trait. The body mass index (BMI) and plasma insulin levels of F2 progeny correlated significantly and positively with plasma leptin levels, suggesting that obesity is associated with insulin resistance. In contrast, systolic pressure did not correlate with BMI, plasma leptin levels, and plasma insulin levels, suggesting that genes underlying the development of hypertension in this intercross are not associated with the development of obesity and insulin resistance. Our results demonstrate that the progeny of NZO and C3H intercrosses are a practical and powerful tool for identifying blood pressure genes and for understanding human polygenic hypertension.