Macula Densa Nitric Oxide Synthase 1 Controls Renin Release and Renin-Dependent Blood Pressure Changes

Fig. 1.. Plasma renin and aldosterone concentration response to dietary salt intake. Plasma renin concentration (PRC) (A) and plasma aldosterone concentration (PAC) (B) were measured at the end of each dietary salt intake. Restriction in sodium intake is associated with markedly elevated plasma renin concentration (PRC) (****p < 0.0001, ***p < 0.001, n = 6–7) and PAC in wild type (WT) mice but not in macula densa-NOS1 knockout (MDNOS1KO) mice (****p < 0.0001, ****p < 0.0001, n = 5). A high salt intake induced decreased PRC in both WT mice and MDNOS1KO mice (****p < 0.0001, ***p < 0.001, n = 5–7). NS, normal salt; LS, low salt; HS, high salt.

Fig. 2.. Glomerular filtration rate (GFR) response to various dietary salt intake. GFRs in conscious WT and MDNOS1KO mice were measured at one day before the end of each dietary salt intake with a single bolus intravenous injection of fluorescein-isothiocyanate (FITC)-sinistrin (****p < 0.0001, n = 6). NS, normal salt; LS, low salt; HS, high salt.

Fig. 3.. Mean arterial pressure (MAP) response to hemorrhagic shock. (A) MAP decreased to about 39 and 31 mmHg after hemorrhagic shock for WT and MDNOS1KO mice, respectively, and returned to baseline within 15 hours. Wild type mice showed quicker recovery in MAP than MDNOS1KO mice (*p < 0.0001 vs. sham; #p < 0.001, MDNOS1KO vs. WT; n = 5). (B) Shows the average MAP values measured in the early phage, partial and total recovery after hemorrhagic shock (****p < 0.0001, **p < 0.01, n = 5).

Fig. 4.. Heart rate (HR) response to hemorrhagic shock. The HRs increased about 300 bpm after hemorrhagic shock for both WT and MDNOS1KO mice and returned to baseline within 10 hours (****p < 0.0001, n = 5).

Fig. 5.. Plasma renin concentration (PRC) response to hemorrhagic shock. Plasma renin concentration (PRC) was measured in all mice at 1, 3, 9, 15 and 20 hours after hemorrhagic shock by radioimmunoassay. Hemorrhagic shock dramatically stimulated the renin release in WT mice, however, there was only a mild increase in PRC in MDNOS1KO mice (*p < 0.0001 WT or MDNOS1KO vs. their respective sham; #p < 0.0001 WT vs. MDNOS1KO; n = 5).