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Microchemical techniques were employed to measure the DNA, contractile proteins, and connective tissue protein composition of 150 micrograms samples of mesenteric and cerebral resistance arteries taken from 25-week-old spontaneously hypertensive (SHR) and control Wistar-Kyoto (WKY) rats. The active and passive mechanical properties of intact resistance arteries also were determined. The DNA content of branches of the posterior cerebral and mesenteric arteries (170 micrometers I.D.) were elevated by nearly 30% in the SHR compared to the WKY. The amounts of actin and myosin when normalized to DNA content were unchanged in SHR mesenteric arteries compared to control, whereas these amounts were decreased by 25% and 49%, respectively, in the SHR cerebral arteries vs control. The functional implications of these contractile protein measurements agreed with determinations of active smooth muscle cell stress-generating capabilities, which were found unchanged in the mesenteric arteries and depressed in the SHR cerebral arteries. Neither the absolute amounts and concentrations (relative to tissue mass) of elastin in mesenteric and cerebral arteries, nor the absolute amounts and concentrations of collagen in the mesenteric artery, were changed in the SHR. However, cerebral artery total collagen was elevated by 31% in the SHR, with no change in collagen concentration between the two strains. Under conditions where the smooth muscle cells were fully relaxed, the internal radii of SHR brain and SHR mesenteric arteries were smaller at all pressures with respect to the WKY. However, only the SHR cerebral arteries were actually less distensible than controls. Thus, it is apparent that hypertension-associated changes in the chemical and mechanical properties of the resistance artery wall vary considerably depending upon which vascular bed is examined. The measurements made in this study suggest that these changes are more pronounced in brain arteries. This finding could be of significance regarding the autoregulatory capability of, and blood pressure distribution within, brain vessels of hypertensive animals.