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Author(s): Yoriko Yamazato [sup.1] , Masanobu Yamazato [sup.2] , Akio Ishida [sup.2] , Jiro Fujita [sup.1] , Yusuke Ohya [sup.2] Author Affiliations: (Aff1) 0000 0001 0685 5104, grid.267625.2, Department of [...], Purpose Inflammation is a feature of lung injury and plays a critical role in pulmonary vascular remodeling. Bone marrow-derived cells (BMCs) have anti-inflammatory properties and favor macrophage differentiation into an alternatively activated regulatory M2 profile. We investigated the effect of autologous BMCs on monocrotaline-induced pulmonary vessel remodeling and lung inflammation in rats, by direct administration into lungs via the airway. Methods BMCs were isolated and plastic-adherent cells were cultured for 3 weeks. 1 week following monocrotaline (60 mg/kg) treatment, fluorescently labeled autologous BMCs (1 x 10.sup.6 cells) or vehicle were administered intratracheally to male Sprague-Dawley rats. 4 weeks following monocrotaline treatment, lung pathology was evaluated. Results Monocrotaline increased pulmonary vessel wall thickness, perivascular infiltration, alveolar septal thickening, and inflammatory cell infiltration including T lymphocytes and monocytes/macrophages in alveolar areas, and also increased mRNA expression of inflammatory-related cytokines including IL-10 in the lung. Intratracheal administration of autologous BMCs prevented pulmonary vessel wall thickening and perivascular infiltration, and increased CD163-positive M2-like macrophages in perivascular areas. BMC administration inhibited the thickening of alveolar septa and reduced monocrotaline-induced inflammatory cell infiltration in lung parenchyma compared with monocrotaline-vehicle-treated-rats. Furthermore, BMCs administration increased expression of CD163-positive cells in perivascular areas and maintained the increased mRNA expression of IL-10. Conclusions Intratracheal administration of autologous BMCs prevented monocrotaline-induced pulmonary vessel remodeling and lung inflammation, at least in part, through induction of alternatively activated macrophages and regulation of the local lung environment toward resolving inflammation.

A chromosome 1 blood pressure quantitative trait locus (QTL) was introgressed from the stroke-prone spontaneously hypertensive rats (SHRSP) to Wistar-Kyoto (WKY) rats. This congenic strain (WKYpch1.0) showed an exaggerated pressor response to both restraint and cold stress. In this study, we evaluated cardiovascular and sympathetic response to an air-jet stress and also examined the role of the brain renin-angiotensin system (RAS) in the stress response of WKYpch1.0. We measured mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to air-jet stress in WKYpch1.0, WKY, and SHRSP. We also examined effects of intracerebroventricular administration of candesartan, an ANG II type 1 receptor blocker, on MAP and HR responses to air-jet stress. Baseline MAP in the WKYpch1.0 and WKY rats were comparable, while it was lower than that in SHRSP rats. Baseline HR did not differ among the strains. In WKYpch1.0, air-jet stress caused greater increase in MAP and RSNA than in WKY. The increase in RSNA was as large as that in SHRSP, whereas the increase in MAP was smaller than in SHRSP. Intracerebroventricular injection of a nondepressor dose of candesartan inhibited the stress-induced pressor response to a greater extent in WKYpch1.0 than in WKY. Intravenous injection of phenylephrine caused a presser effect comparable between WKYpch1.0 and WKY. These results suggest that the chromosome 1 blood pressure QTL congenic rat has a sympathetic hyperreactivity to an air-jet stress, which causes exaggerated pressor responses. The exaggerated response is at least partly mediated by the brain RAS. renal sympathetic nerve activity; Wistar-Kyoto rat; stroke-prone spontaneously hypertensive rats; brain renin-angiotensin system

Yamazato, Masanobu, Atsushi Sakima, Jun Nakazato, Shogo Sesoko, Hiromi Muratani, and Koshiro Fukiyama. Hypotensive and sedative effects of clonidine injected into the rostral ventrolateral medulla of conscious rats. Am J Physiol Regulatory Integrative Comp Physiol 281: R1868-R1876, 2001.--We examined the effects of clonidine injected unilaterally into the rostral ventrolateral medulla (RVLM) of conscious, unrestrained rats. We also examined whether the local [[alpha].sub.2]-adrenoceptor mechanism contributed to the action of clonidine injected into the RVLM. Injection of clonidine but not vehicle solution significantly decreased the mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious, unrestrained rats as well as in propofol-anesthetized rats. The frequency of natural behavior was significantly lower after clonidine injection than after vehicle injection. The depressor and sympathoinhibitory responses were significantly larger in the propofol-anesthetized rats than in the conscious rats. Coinjection of a selective [[alpha].sub.2]-adrenoceptor antagonist, 2-methoxyidazoxan, with clonidine into the RVLM significantly attenuated the depressor, bradycardiac, sympathoinhibitory, and sedative effects of clonidine injected alone. In conclusion, clonidine injected into the RVLM decreased MAP, HR, and RSNA and caused sedation in conscious, unrestrained rats. The action of clonidine in the RVLM was at least partly mediated by [[alph]a.sub.2]-adrenoceptor mechanisms. blood pressure; [[alpha].sub.2]-adrenoceptor; renal sympathetic nerve activity; natural behavior Received 29 December 2000; accepted in final form 7 August 2001

Research was conducted to determine whether inhibition of brain nitric oxide synthase (NOS) increases blood pressure (BP) in normotensive rats and, if true, whether the BP elevation is improved by salt loading. Findings indicated that in normotensive Sprague-Dawley (SD) rats, prolonged inhibition of NOS in the brain results in increased blood pressure. However, even when combined with salt loading, brain NOS inhibition may not be enough to cause definite hypertension in normotensive SD rats.

Cardiovascular parameters and renal sympathetic nerve activity were monitored in male Sprague-Dawley rats before and after microinjection of the alpha2 adrenoreceptor agonist clonidine at the caudal ventrolateral medulla (CVLM) with or without receptor blocking to determine the contribution of the alpha2 adrenoreceptor at the CVLM to autonomic regulation. Results suggest that clonidine inhibits neurons in the CVLM.

Stimulation of α2-adrenoceptor/I1-imidazoline receptors in the rostral ventrolateral medulla decreases the blood pressure via sympathoinhibition. However, alteration of receptor responses in genetically hypertensive rats remains unclear. We examined cardiovascular responses of α2-adrenoceptor/I1-imidazoline receptor agonist and antagonists microinjected into the rostral ventrolateral medulla of conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Injection of 2-nmol clonidine—an α2-adrenoceptor/I1-imidazoline receptor agonist—unilaterally into the rostral ventrolateral medulla decreased the blood pressure, heart rate, and renal sympathetic nerve activity; the responses were significantly enhanced in spontaneously hypertensive rats than in Wistar Kyoto rats. Co-injection of 2-nmol 2-methoxyidazoxan (a selective α2-adrenoceptor antagonist) or 2-nmol efaroxan (an I1-receptor antagonist) with 2 nmol of clonidine attenuated the hypotensive and bradycardic effects of clonidine-only injection. Injection of 2-methoxyidazoxan alone increased the blood pressure and heart rate in spontaneously hypertensive rats, but not in Wistar Kyoto rats. These results suggest enhanced responsiveness of α2-adrenoceptor/I1-imidazoline receptors in the rostral ventrolateral medulla of spontaneously hypertensive rats. [ABSTRACT FROM AUTHOR]