Renal proximal tubule (RPT) dopamine D
1
-like receptors (D
1
R) and angiotensin II type-2 receptor (AT
2
R) inhibit sodium reabsorption and counter regulate the renin angiotensin systems AT
1
R which stimulates sodium reabsorption. Salt sensitivity of blood pressure (SS) is defined as a ≥7-mmHg rise in blood pressure following a week of daily consumption of 350 mM sodium chloride (NaCl). Inverse salt sensitivity (ISS) is defined as a ≥7-mm Hg increase in blood pressure (BP) after a week of 10 mM NaCl/day. Salt resistant controls were defined as < 7mM Hg change in BP whether on 10 or 350mmHg NaCl/day for one week. Previously, we demonstrated that D
1
R RPT membrane recruitment was inversely proportional to an individual’s degree of BP increase on a 350 mM diet. We hypothesize that the degree of salt sensitivity of blood pressure would be inversely correlated with the recruitment of the AT
2
R to the plasma membrane induced by NaCl. Immunostaining shows that D
1
R was distributed in a fine granular manner throughout the whole plasma membrane, while AT
2
R shows a punctate pattern in both urine-derived SR and ISS RPTCs. There was no difference of basal D
1
R or AT
2
R expression. Increasing cell NaCl (monensin ionophore 10 μM, 1 hour) resulted in a significantly more AT
2
R and D
1
R(control) recruitment to cell surface in ISS cells than in SR cells (D
1
R: MON/VEH: SR, 1.032 ± 0.056, n=4; ISS, 1.537 ± 0.097, n=4; t-test, p<0.01; AT
2
R :MON/VEH: SR, 0.923 ± 0.063, n=3; ISS, 1.28 ± 0.106, n=3; t-test, p<0.05). Because ISS individuals present to the medical system with elevated blood pressure while on a low salt diet, they are often misdiagnosed as hypertensive. As our studies were conducted on RPT cells isolated from individual's urine, the D
1
R and AT
2
R response may contribute to the diagnosis of ISS individuals with elevated blood pressure while on a 10 mM salt diet, and provide better understanding on the etiology of ISS.
Membrane hyperpolarization and salt sensitivity induced by deletion of PMP3, a highly conserved small protein of yeast plasma membrane
