Intracellular pH in human resistance arteries in essential hypertension.
To investigate intracellular pH (pHi) 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 pHi and the changes in pHi observed during isometric contractions initiated by agonists could be recorded. Resting pHi 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 pHi homeostasis but that neither system was overactive in hypertension (pHi change with EIPA in vessels from hypertensive versus control subjects was -0.11 +/- 0.02 and 0.13 +/- 0.03 pH units, respectively, and pHi 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 pHi. With norepinephrine this fall was significantly attenuated in vessels from hypertensive patients. These results fail to provide evidence for raised pHi 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.
Izzard
A S
AS
Department of Medicine, University of Leicester, UK.
Cragoe
E J
EJ
Heagerty
A M
AM
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000273:Adipose Tissue / Q000098:blood supply; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001158:Arteries / Q000502:physiology*; D001639:Bicarbonates; D001692:Biological Transport; D002138:Calibration; D002352:Carrier Proteins / Q000502:physiology; D005260:Female; D005452:Fluoresceins; D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012867:Skin / Q000098:blood supply; D017923:Sodium-Hydrogen Exchangers; D014655:Vascular Resistance / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D001639:Bicarbonates; D002352:Carrier Proteins; D005452:Fluoresceins; D017923:Sodium-Hydrogen Exchangers; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000584:Amiloride; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium; C039614:ethylisopropylamiloride; D009638:Norepinephrine