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.
Moderate salt restriction effectively lowers blood pressure and degree of salt sensitivity is predicted by plasma renin in Swedish subjects with normal and slightly elevated blood pressure
