Volume 20, Issue 2, Pages 159-164 (April 2013) Mismatch between peripheral and central demands in salt-sensitive hypertensive Dahl rats  Yasuhiro Nishida, Megumi Tandai-Hiruma, Takehito Kemuriyama, Kohsuke Hagisawa  Pathophysiology  Volume 20, Issue 2, Pages 159-164 (April 2013) DOI: 10.1016/j.pathophys.2012.12.002 Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 1 DS: Dahl salt-sensitive rats; DR: Dahl salt-resistant rats; 8%: fed 8% NaCl diet (high salt diet); 0.4%: fed 0.4% NaCl diet (regular diet); SAP: systolic arterial pressure measured with the tail cuff method; age: rat age; *p<0.005 vs. DS-0.4%; †p<0.05 vs. the initial (8-week) value for DS-8%. The high salt diet produced marked hypertension in Dahl salt-sensitive rats. See details in Ref. [5]. Pathophysiology 2013 20, 159-164DOI: (10.1016/j.pathophys.2012.12.002) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 2 DS-8%, DS-0.4%, DR-8%, DR-0.4%: see Fig. 1 legend. Contraction: contractile activity (g) evoked by norepinephrine (NE 10−8 to 10−6M) in aortic rings of the rats in the four experimental groups (n=10–12 each), as measured with the magnus method. ED50: half maximal response; Emax: maximum response; *p<0.005 high-salt vs. low-salt DS rats. Arteries from salt-sensitive hypertensive rats contract stronger than arteries from the other groups of rats. See details in Ref. [5]. Pathophysiology 2013 20, 159-164DOI: (10.1016/j.pathophys.2012.12.002) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 3 S 0.4%: Dahl salt-sensitive rats fed a regular diet; S 8%: Dahl salt-sensitive rats fed a high-salt diet; Oc with bar line: gradual caval occlusion in which the inferior vena cava was occluded in a ramp manner with a perivascular occluder. AP: arterial pressure; MAP: mean arterial pressure; HR: heart rate; RSNA: renal sympathetic nerve activity; meanRSNA: mean RSNA expressed as a %; aCSF icv: intaracerebroventricular infusion of artificial cerebrospinal fluid (control groups); SMTC icv: intracerebroventricular infusion of 50nmol S-methyl-l-thiocitrulline, an nNOS inhibitor (details in Ref. [20]). Each arrow indicates a peak response of mean RSNA to a ramp decrease in MAP by caval occlusion. RSNA signals after these peak responses were produced by animal movements because of hypotension. Both resting RSNA and the peak response obtained by the release of baroreflex-mediated negative feedback inhibition (baroreceptor-unloaded RSNA, which indicates central sympathetic activity generated before baroreflex inhibition), were markedly increased after SMTC infusion (see details in Ref. [20]). See Table 1 for resting values. Pathophysiology 2013 20, 159-164DOI: (10.1016/j.pathophys.2012.12.002) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 4 Distribution of neurons containing neuronal nitric oxide synthase (nNOS neurons) in rat brain, modified from Ref. [26]. Curved bands indicate areas with higher numbers of nNOS neurons in salt-sensitive hypertensive rats compared with salt-sensitive normotensive rats. Grey text indicates parts of the sympathetic center. Numbers indicate the plate number in the book by George Paxison (Ref. [27]). PVN: paraventricular nucleus; SON: supraoptic nucleus; DMH: dorsomedial hypothalamus; PAG: periaquaductal gray matter; PB: parabrachial nucleus; NTS: nucleus tractus solitarius; RVLM: rostral ventrolateral medulla; CVLM: caudal ventrolateral medulla; CPA: caudal pressor area; IML: intermediolateral column. Pathophysiology 2013 20, 159-164DOI: (10.1016/j.pathophys.2012.12.002) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 5 Putative characteristics of the blood pressure control system and the target organs in Dahl salt-sensitive hypertension. Baro: arterial baroreceptors; CNS: central nervous system; N inside an airplane: neural outputs from the CNS; H inside a ship: Humoral outputs from the CNS; H: heart; TPR: total peripheral resistance; VOL: circulating blood volume; AP: arterial pressure; PSN: peripheral sympathetic nerves. In Dahl hypertensive rats, the sympathetic center becomes pathophysiologically hyper-reactive, concomitant with compensatory upregulated activity in nNOS neuron-mediated inhibitory systems of the central sympathetic center, which results in hyper-reactivity in peripheral sympathetic activity. On the other side of the target organs, the kidney functions abnormally, and the peripheral vascular system shows hypertrophy and abnormally functioning endothelium. Pathophysiology 2013 20, 159-164DOI: (10.1016/j.pathophys.2012.12.002) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions