Comparison between C57BL/6N and C57BL/6J for their systolic blood pressure and heart rate responses to various salt challenges measured by NIBP.

<p>Measurements were made during the dark periods of a modified light/dark cycle. NS = normal salt diet (n = 20 and n = 20, for C57BL/6N and C57BL/6J respectively), LS = low salt diet (n = 20 and n = 20, for C57BL/6N and C57BL/6J respectively), HS = high Na⁺/normal K⁺ diet (n = 9 and n = 10, for C57BL/6N and C57BL/6J respectively) and HS/LK = high Na⁺/low K⁺ diet (n = 9 and n = 10, for C57BL/6N and C57BL/6J respectively). One-way ANOVA per light phase followed by Tukey Kramer’s post-hoc test; #: p<0.05 HS/LK compared to HS.</p

Comparison between C57BL/6N and C57BL/6J for their mean blood pressure and heart rate responses to various salt challenges.

<p>Mice were monitored with telemetry during the dark (A, B) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17 and n = 17, for C57BL/6N and C57BL/6J respectively), LS = low salt diet (n = 15 and n = 17, for C57BL/6N and C57BL/6J respectively), HS = high Na⁺/normal K⁺ diet (n = 8 and n = 8, for C57BL/6N and C57BL/6J respectively) and HS/LK = high Na⁺/low K⁺ diet (n = 6 and n = 9, for C57BL/6N and C57BL/6J respectively). One-way ANOVA per light phase followed by Tukey’s post-hoc test; *: p<0.05 compared to NS diet; #: p<0.05 HS/LK compared to HS.</p

Effects of high-salt/normal potassium and high-salt/low potassium on mean blood pressure and heart rate in C57BL/6N mice.

<p>Mice were monitored with telemetry in the dark (A, B, C) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17), LS = low salt diet (n = 15), HS = high Na⁺/normal K⁺ diet (n = 8) and HS/LK = high Na⁺/low K⁺ diet (n = 6). One-way ANOVA per light phase followed by Tukey’s post-hoc test; *: p<0.05 compared to NS diet; #: p<0.05 HS/LK compared to HS.</p

Effects of various salt challenges on mean blood pressure and heart rate in C57BL/6N male mice.

<p>Mice were monitored with telemetry and placed in a standard (A, C) or modified light/dark cycle (B, D). NS = normal salt diet (n = 12 and n = 17, for the standard and modified light cycle respectively), LS = low salt diet (n = 11 and n = 15, for the standard and modified light cycle respectively), HS = high Na⁺/normal K⁺ diet (n = 5 and n = 6, for the standard and modified light cycle respectively). One-way ANOVA per light phase followed by Tukey’s post-hoc test; *: p<0.05 compared to NS diet.</p

Plasma ion, aldosterone and renin activity measurements in C57BL/6N and C57BL/6J male mice.

<p>Plasma ion, aldosterone and renin activity measurements in C57BL/6N and C57BL/6J male mice.</p

Effect of high salt diets on the circadian blood pressure variations in C57BL/6N and C57BL/6J mice under a reverse light/dark cycle.

<p>2.5 days continuous telemetric recordings of systolic blood pressure after 2 weeks of NS, HS or HS/LK diet challenge. A) n = 8 per group B) n = 6 per group C) n = 8 per group D) n = 9 per group. Two-way ANOVA followed by Sidak’s post-hoc test *: p<0.05 for interaction.</p

Sodium and potassium levels in urine and plasma in C57BL/6N.

<p>Sodium and potassium levels in urine and plasma in C57BL/6N.</p

Regulator of G-Protein Signaling 18 Controls Both Platelet Generation and Function

<div><p>RGS18 is a myeloerythroid lineage-specific regulator of G-protein signaling, highly expressed in megakaryocytes (MKs) and platelets. In the present study, we describe the first generation of a RGS18 knockout mouse model (RGS18-/-). Interesting phenotypic differences between RGS18-/- and wild-type (WT) mice were identified, and show that RGS18 plays a significant role in both platelet generation and function. RGS18 deficiency produced a gain of function phenotype in platelets. In resting platelets, the level of CD62P expression was increased in RGS18-/- mice. This increase correlated with a higher level of plasmatic serotonin concentration. RGS18-/- platelets displayed a higher sensitivity to activation <i>in vitro</i>. RGS18 deficiency markedly increased thrombus formation <i>in vivo</i>. In addition, RGS18-/- mice presented a mild thrombocytopenia, accompanied with a marked deficit in MK number in the bone marrow. Analysis of MK maturation <i>in vitro</i> and <i>in vivo</i> revealed a defective megakaryopoiesis in RGS18-/- mice, with a lower bone marrow content of only the most committed MK precursors. Finally, RGS18 deficiency was correlated to a defect of platelet recovery <i>in vivo</i> under acute conditions of thrombocytopenia. Thus, we highlight a role for RGS18 in platelet generation and function, and provide additional insights into the physiology of RGS18.</p></div

RGS18-/- mice present a defective thrombopoiesis after acute thrombocytopenia.

<p>(A) Complement-mediated immune thrombocytopenia. 10-week-old WT (n = 8; black circle) and RGS18-/- mice (n = 8; open circle) were given a sterile intraperitoneal injection of anti-mouse αGpIb antibody (2 µg/g of mouse) at T0 (Arrow). Platelet counts were measured at 4, 48, 72, 96, and 168 hours after injection. (B) Busulfan-induced thrombocytopenia. Busulfan was injected to 9/13-week-old WT (n = 15; black circle) and RGS18-/- mice (n = 14; open circle) intraperitoneally at 30 mg/kg (day 0; arrow). Platelet counts were measured at 7, 11, 15, and 24 days after injection. *P<.05; **P<.01; ***P<.001.</p

RGS18 deficiency increases thrombus formation at sites of arterio-venous shunt <i>in vivo</i>.

<p>An arterio-venous shunt was achieved as described on 11/13-week-old WT and RGS18-/- mice (n = 14 per group) and thrombus weight was determined after 10 minutes of blood circulation. *P<.05.</p