INTRACELLULAR PH IN HUMAN RESISTANCE ARTERIES IN ESSENTIAL-HYPERTENSION

To investigate intracellular pH (pH(i)) in human resistance arteries in essential hypertension, vessels were obtained from small biopsies of skin and subcutaneous fat from 14 untreated patients, and the results were compared with those from 14 matched normotensive control volunteers. Segments of isolated resistance arteries were mounted in a myograph and loaded with the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Fluorescence signals were monitored using a series of barrier filters and chromatic beam splitters. In this way both resting pH(i) and the changes in pH(i) observed during isometric contractions initiated by agonists could be recorded. Resting pH(i) was not different in vessels from hypertensive patients (hypertensive, 7.24 +/- 0.06 versus control, 7.25 +/- 0.04 pH units). The application of ethylisopropylamiloride (EIPA) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) demonstrated that both Na+-H+ exchange and bicarbonate-dependent membrane mechanisms contributed to pH(i) homeostasis but that neither system was overactive in hypertension (pH(i) change with EIPA in vessels from hypertensive versus control subjects was -0.11 +/- 0.02 and 0.13 +/- 0.03 pH units, respectively, and pH(i) change with DIDS in vessels from hypertensive versus control subjects was -0.097 +/- 0.05 and -0.091 +/- 0.03 pH units, respectively). The application of norepinephrine or 125 mM K+ solution induced contraction in the arterial segments with an accompanying fall in pH(i). With norepinephrine this fall was significantly attenuated in vessels from hypertensive patients. These results fail to provide evidence for raised pH(i) in resistance arteries in human essential hypertension, and contrary to previous reports in circulating blood cells, Na+-H+ exchange is not overactive in the vessels of such patients.