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In order to investigate whether resistance arterioles from spontaneously hypertensive rats (SHR) were more alkaline than those from Wistar-Kyoto rats (WKY), mesenteric arterioles were mounted in a myograph and loaded with the pH-sensitive dye 2,7-bis (carboxyethyl)5,6-carboxyfluorescein (BCECF). At 5 weeks of age the arterioles from SHR were significantly more alkaline compared with WKY vessels, at a time when the blood pressure was rising and media: lumen ratio was increasing in the hypertension-prone animals. At 12 weeks this difference was not present due to a non-significant rise in intracellular pH in WKY arterioles. Activation of the vessels with high K+ depolarizing solution or noradrenaline induced an acid change in pH but no subsequent alkalinization was apparent. These results suggest that resistance arterioles from SHR are more alkaline than WKY vessels when the blood pressure is rising and their structural architecture is being modified, and the alkaline cytoplasmic pH may be contributing to the generation of the structural excess seen in these vessels in established hypertension.