Reduced Na-K-Cl cotransport in vascular smooth muscle cells from spontaneously hypertensive rats.
We have previously demonstrated the presence of a prominent, cyclic nucleotide-sensitive Na-K-Cl cotransport in vascular smooth muscle cells (VSMC). Others have observed that Na-K-Cl cotransport levels are reduced in erythrocytes of patients with essential hypertension and have proposed that a defect in this Na transport system may play a role in the pathogenesis of the disease. However, such a defect has not been demonstrated in the putative target tissue for essential hypertension, i.e., the VSMC. In the present study, we compared Na-K-Cl cotransport of VSMC from spontaneously hypertensive rats (SHR) with Na-K-Cl cotransport of VSMC from normotensive Wistar-Kyoto rats (WKY). We found that Na-K-Cl cotransport of SHR VSMC is significantly reduced relative to that of WKY VSMC (3.09 vs. 4.39 mumol K.g protein-1.min-1). The apparent ion affinities for Na-K-Cl cotransport of SHR VSMC did not differ from those determined for WKY VSMC. Furthermore, cyclic nucleotide regulation of cotransport also appeared to be the same for the two types of VSMC. In contrast, maximal saturable binding of [3H]bumetanide observed in SHR VSMC was markedly reduced compared with that of WKY VSMC, but the Kd values were similar. Our data suggest that the reduction in cotransport observed in SHR VSMC is the result of a decrease in the number of available cotransport sites.
O'Donnell
M E
ME
Department of Biological Chemistry and Structure, University of Health Sciences, Chicago Medical School, Illinois 60064.
Owen
N E
NE
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters; D013045:Species Specificity
D002352:Carrier Proteins; D002712:Chlorides; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D012964:Sodium; D006152:Cyclic GMP; D011188:Potassium; D009638:Norepinephrine