Search PubMed⌕ Search

Biomedical subjects

Kenji Sunagawa

Publications and source records attributed to Kenji Sunagawa.

At least 37 records · Page 2Linked to original sources
PubMed2006

Matrix metalloproteinases are involved in mechanical stretch-induced activation of skeletal muscle satellite cells.

When skeletal muscle is stretched or injured, myogenic satellite cells are activated to enter the cell cycle. This process depends on nitric oxide (NO) production, release of hepatocyte growth factor (HGF) from the extracellular matrix, and presentation of HGF to the c-met receptor. Experiments reported herein provide new evidence that matrix metalloproteinases (MMPs) are involved in the NO-dependent release of HGF in vitro. When rat satellite cells were treated with 10 ng/ml recombinant tissue inhibitor-1 of MMPs (TIMP-1) and subjected to treatments that induce activation in vitro, i.e., sodium nitroprusside (SNP) of an NO donor or mechanical cyclic stretch, the activation response was inhibited. In addition, conditioned medium generated by cultures treated with TIMP-1 plus SNP or mechanical stretch failed to activate cultured satellite cells and did not contain HGF. Moreover, NO(x) assay demonstrated that TIMP-1 does not impair NO synthase activity of stretched satellite cell cultures. Therefore, results from these experiments provide strong evidence that MMPs mediate HGF release from the matrix and that this step in the pathway is downstream from NO synthesis.

Animals↗
PubMed2006

Extracorporeal cardiac shock wave therapy ameliorates myocardial ischemia in patients with severe coronary artery disease.

OBJECTIVE: Prognosis of severe coronary artery disease with no indication of percutaneous coronary intervention or coronary artery bypass grafting remains poor. We have recently demonstrated that shock wave therapy effectively induces neovascularization and improves myocardial ischemia in a porcine model in vivo. METHODS: With permission from the Ethical Committee of our Institute, we treated nine patients with end-stage coronary artery disease with no indication of percutaneous coronary intervention or coronary artery bypass grafting (55-82 years old, five men and four women) with our cardiac shock wave therapy (200 shots/spot at 0.09 mJ/mm for 20-40 spots, 3 times a week/series). We followed-up the patients at 1, 3, 6, and 12 months after the therapy to examine the amelioration of myocardial ischemia. When needed, shock wave therapy was performed up to three series at 0, and 1, 3 or 6 months. RESULTS: The cardiac shock wave therapy improved symptoms (Canadian Cardiovascular Society functional class score, from 2.7+/-0.2 to 1.8+/-0.2, P<0.01) and reduced nitroglycerin use (from 5.4+/-2.5 to 0.3+/-0.3/week, P<0.05). The treatment also improved myocardial perfusion as assessed by dipyridamole stress thallium scintigraphy (severity score, 25.2+/-7.2% improvement, P<0.05; extent score, 23.3+/-9.0% improvement, P=0.10; washout rate, 20+/-3 to 34+/-3, P<0.05). Myocardial perfusion was improved only in the ischemic area treated with the therapy. These beneficial effects persisted for 12 months. No procedural complications or adverse effects were noted. CONCLUSION: These results indicate that our extracorporeal cardiac shock wave therapy is an effective and non-invasive treatment for end-stage coronary artery disease, although further careful evaluation is needed.

Aged↗
PubMed2006

Angiotensin II type 1 receptor blocker attenuates exacerbated left ventricular remodeling and failure in diabetes-associated myocardial infarction.

Diabetes mellitus adversely affects the outcomes in patients with myocardial infarction (MI), due in part to the exacerbation of left ventricular (LV) remodeling. Although angiotensin II type 1 receptor blocker (ARB) has been demonstrated to be effective in the treatment of heart failure, information about the potential benefits of ARB on advanced LV failure associated with diabetes is lacking. To induce diabetes, male mice were injected intraperitoneally with streptozotocin (200 mg/kg). At 2 weeks, anterior MI was created by ligating the left coronary artery. These animals received treatment with olmesartan (0.1 mg/kg/day; n = 50) or vehicle (n = 51) for 4 weeks. Diabetes worsened the survival and exaggerated echocardiographic LV dilatation and dysfunction in MI. Treatment of diabetic MI mice with olmesartan significantly improved the survival rate (42% versus 27%, P < 0.05) without affecting blood glucose, arterial blood pressure, or infarct size. It also attenuated LV dysfunction in diabetic MI. Likewise, olmesartan attenuated myocyte hypertrophy, interstitial fibrosis, and the number of apoptotic cells in the noninfarcted LV from diabetic MI. Post-MI LV remodeling and failure in diabetes were ameliorated by ARB, providing further evidence that angiotensin II plays a pivotal role in the exacerbated heart failure after diabetic MI.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

A third-generation, long-acting, dihydropyridine calcium antagonist, azelnidipine, attenuates stent-associated neointimal formation in non-human primates.

BACKGROUND: Calcium antagonists have been shown to reduce atherogenesis and improve clinical outcomes in atherosclerotic vascular disease. No study has so far, however, addressed the effects of calcium antagonists on stent-associated neointimal formation. We therefore investigated whether a third-generation calcium antagonist, azelnidipine, attenuates in-stent neointimal formation in non-human primates. METHOD: Male cynomolgus monkeys were fed a high cholesterol diet for 4 weeks, and were randomly assigned to three groups: a vehicle group and two other groups treated with azelnidipine at 3 and 10 mg/kg per day for an additional 24 weeks (n = 12 each). Multi-link stents were then implanted in the iliac artery. RESULTS: Azelnidipine at the high dose reduced neointimal thickness (0.25 +/- 0.02 versus 0.19 +/- 0.02 mm; P < 0.05). Azelnidipine also reduced local oxidative stress and monocyte chemoattractant protein 1 (MCP-1) expression. No difference was found between the three groups in the degrees of injury score, inflammation score, plaque neovascularization, or plasma lipid levels. Azelnidipine also reduced MCP-1-induced proliferation/migration of vascular smooth muscle cells in vitro. CONCLUSIONS: This study demonstrated for the first time that azelnidipine attenuates in-stent neointimal formation associated with the reduced expression of MCP-1 and smooth muscle proliferation/migration in the neointima. These data in non-human primates suggest potential clinical benefits of azelnidipine as a 'vasculoprotective calcium antagonist' in patients undergoing vascular interventions.

Aged↗
PubMed2006

CAMP-response element-binding protein mediates tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in endothelial cells.

Hypertension causes endothelial dysfunction, which plays an important role in atherogenesis. The vascular cell adhesion molecule-1 (VCAM-1) contributes to atherosclerotic lesion formation by recruiting leukocytes from blood into tissues. Tumor necrosis factor-alpha (TNFalpha) induces endothelial dysfunction and VCAM-1 expression in endothelial cells (ECs). We examined whether the cAMP-response element binding protein (CREB), a transcription factor that mediates cytokine expression and vascular remodeling, is involved in TNFalpha-induced VCAM-1 expression. TNFalpha induced phosphorylation of CREB with a peak at 15 min of stimulation in a dose-dependent manner in bovine aortic ECs. Pharmacological inhibition of p38 mitogen-activated protein kinase (p38-MAPK) inhibited TNFalpha-induced CREB phosphorylation. Adenovirus-mediated overexpression of a dominant-negative form of CREB suppressed TNFalpha-induced VCAM-1 and c-fos expression. Although activating protein 1 DNA binding activity was attenuated by overexpression of dominant negative CREB, nuclear factor-kappaB activity was not affected. Our results suggest that the p38-MAPK/CREB pathway plays a critical role in TNFalpha-induced VCAM-1 expression in vascular endothelial cells. The p38MAPK/CREB pathway may be a novel therapeutic target for the treatment of atherosclerosis.

Adenoviridae↗
PubMed2006

Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats.

Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP.

Amlodipine↗
PubMed2006

[Medical nanodevices].

Development of implantable medical nanodevices enables us continuous automatic treatment of patients from inside of their body. Bionic devices, interfacing with neural systems and substituting native functions, such as bionic pacemaker, bionic pressure controller are candidates to miniaturize. For such miniaturization, efforts to reduce size of power supply (e.g., biological fuel cell) and to establish reliable high-throughput, low power telecommunication (e.g., spread spectrum telecommunication) are required. Simple devices such as pacemakers would benefit from miniaturization by lowering invasion and by developing a new usage such as ventricular resynchronization.

Animals↗
PubMed2005

Automated drug delivery system to control systemic arterial pressure, cardiac output, and left heart filling pressure in acute decompensated heart failure.

Pharmacological support with inotropes and vasodilators to control decompensated hemodynamics requires strict monitoring of patient condition and frequent adjustments of drug infusion rates, which is difficult and time-consuming, especially in hemodynamically unstable patients. To overcome this difficulty, we have developed a novel automated drug delivery system for simultaneous control of systemic arterial pressure (AP), cardiac output (CO), and left atrial pressure (Pla). Previous systems attempted to directly control AP and CO by estimating their responses to drug infusions. This approach is inapplicable because of the difficulties to estimate simultaneous AP, CO, and Pla responses to the infusion of multiple drugs. The circulatory equilibrium framework developed previously (Uemura K, Sugimachi M, Kawada T, Kamiya A, Jin Y, Kashihara K, and Sunagawa K. Am J Physiol Heart Circ Physiol 286: H2376-H2385, 2004) indicates that AP, CO, and Pla are determined by an equilibrium of the pumping ability of the left heart (SL), stressed blood volume (V), and systemic arterial resistance (R). Our system directly controls SL with dobutamine, V with dextran/furosemide, and R with nitroprusside, thereby controlling the three variables. We evaluated the efficacy of our system in 12 anesthetized dogs with acute decompensated heart failure. Once activated, the system restored SL, V, and R within 30 min, resulting in the restoration of normal AP, CO, and Pla. Steady-state deviations from target values were small for AP [4.4 mmHg (SD 2.6)], CO [5.4 ml x min(-1) x kg(-1) (SD 2.4)] and Pla [0.8 mmHg (SD 0.6)]. In conclusion, by directly controlling the mechanical determinants of circulation, our system has enabled simultaneous control of AP, CO, and Pla with good accuracy and stability.

Animals↗
PubMed2005

Postexercise VO2 "Hump" phenomenon as an indicator for inducible myocardial ischemia in patients with acute anterior myocardial infarction.

OBJECTIVES: At exercise testing with respiratory gas analysis in patients with inducible myocardial ischemia, we have occasionally observed abnormal transient oxygen uptake (VO2) components with a characteristic "Hump"-shaped morphology early after exercise, which may serve as an index for inducible ischemia. We examined this hypothesis in patients with anterior q-wave myocardial infarction in whom the accuracy to identify ischemia by exercise ECG is limited. DESIGN: From patients with acute anterior q-wave infarction but without clinically overt heart failure who underwent pre-discharge exercise testing, we examined patients with (Group-I, n = 30) and without (Group-N, n = 29) inducible ischemia. To identify "Hump", postexercise VO2 (up to 4 min) standardized for peak VO2 was exponentially fitted with use of peak VO2 and VO2 of 90-240 s, yielding "expected VO2". "D-curve" was obtained by subtracting "expected VO2" from measured VO2. RESULTS: Although exercise-induced ST depressions more frequently appeared in Group-I (27%) than in Group-N (3%, p < 0.05), the prevalence was low. D-curve peaked later (p < 0.01) and its value was greater (p < 0.05) in Group-I than in Group-N. When "Hump" was defined to be present if D-curve peaked > or =40 s and its peak value > or =15%, it was far more frequently found in Group-I (n = 17/30) than in Group-N (n = 1/29, p < 0.01). Thus, "Hump" could diagnose inducible ischemia with a sensitivity of 57% and a specificity of 97%. CONCLUSIONS: Although not highly sensitive, postexercise VO2 "Hump" with its peak occurring around 60 s after exercise is a specific marker for inducible ischemia. The identification may be useful, particularly in patients with limited accuracy of exercise ECG such as those with q-wave anterior infarction.

Exercise Test↗
PubMed2005

Blockade of NF-kappaB ameliorates myocardial hypertrophy in response to chronic infusion of angiotensin II.

OBJECTIVE: Nuclear factor (NF)-kappaB is a key transcription factor that regulates inflammatory processes. In the present study, we assessed the hypothesis that blockade of NF-kappaB may ameliorate ventricular hypertrophy in response to chronic infusion of angiotensin II. METHODS: Mice with targeted disruption of the p50 subunit of NF-kappaB (KO) were used to block the activation of NF-kappaB. Male KO and age-matched wild-type (WT) mice were chronically infused with angiotensin II at the rate of 0.2 (low dose) or 2 microg/kg/min (high dose) for 4 weeks. RESULTS: High- but not low-dose angiotensin II significantly increased systemic blood pressure and left ventricular weight in WT mice. In contrast, although the pressor response was slightly but significantly augmented, the hypertrophic effect of angiotensin II was significantly attenuated in KO mice. The attenuated hypertrophic responsiveness was confirmed histologically (cross-sectional area) and transcriptionally (atrial natriuretic peptide). Echocardiography revealed no evidence of cardiac dysfunction in angiotensin II-treated KO mice. Although phosphorylation of MAPKs, including ERK, JNK, or p38-MAPK, was not affected after 4 weeks of angiotensin II treatment in WT mice, phosphorylation of JNK was specifically abrogated in KO mice. Angiotensin II increased myocardial expression of proinflammatory cytokines and chemokines in WT mice, while expression of TNF-alpha and RANTES was paradoxically augmented in KO mice. CONCLUSION: Blockade of NF-kappaB activation attenuated myocardial hypertrophy without deteriorating cardiac function. NF-kappaB may play an important role in cardiac hypertrophy and remodeling besides promoting inflammation.

Angiotensin II↗
PubMed2005

Vagal stimulation suppresses ischemia-induced myocardial interstitial norepinephrine release.

Although electrical vagal stimulation exerts beneficial effects on the ischemic heart such as an antiarrhythmic effect, whether it modulates norepinephrine (NE) and acetylcholine (ACh) releases in the ischemic myocardium remains unknown. To clarify the neural modulation in the ischemic region during vagal stimulation, we examined ischemia-induced NE and ACh releases in anesthetized and vagotomized cats. In a control group (VX, n = 8), occlusion of the left anterior descending coronary artery increased myocardial interstitial NE level from 0.46+/-0.09 to 83.2+/-17.6 nM at 30-45 min of ischemia (mean+/-SE). Vagal stimulation at 5 Hz (VS, n = 8) decreased heart rate by approximately 80 beats/min during the ischemic period and suppressed the NE release to 24.4+/-10.6 nM (P < 0.05 from the VX group). Fixed-rate ventricular pacing (VSP, n=8) abolished this vagally mediated suppression of ischemia-induced NE release. The vagal stimulation augmented ischemia-induced ACh release at 0-15 min of ischemia (VX: 11.1+/-2.1 vs. VS: 20.7+/-3.9 nM, P < 0.05). In the VSP group, the ACh release was not augmented. In conclusion, vagal stimulation suppressed the ischemia-induced NE release and augmented the initial increase in the ACh level. These modulations of NE and ACh levels in the ischemic myocardium may contribute to the beneficial effects of vagal stimulation on the heart during acute myocardial ischemia.

Acetylcholine↗
PubMed2005

Selective detection of a catecholamine against electroactive interferents using an interdigitated heteroarray electrode consisting of a metal oxide electrode and a metal band electrode.

We developed an interdigitated array electrode (IDAE) consisting of a metal oxide electrode and a metal band heteroelectrode and employed it for the selective detection of catecholamines. We used an indium-tin oxide (ITO) film as the oxidation electrode of the IDAE because the ITO was able to suppress response currents from L-ascorbic acid (AA) and uric acid (UA), which are major electroactive interferents in biological fluids. However, the ITO film also suppresses the reduction of quinones including oxidized catecholamines. We developed a simple technique for fabricating our hetero IDAE, which also preserves the electrochemical properties of the ITO. When we compared hetero ITO-gold, homo ITO-ITO, and carbon-carbon IDAEs, we found that the hetero IDAE provided both high sensitivity and selectivity for DA detection. We achieved high selectivities for DA against AA and UA. The ratios of the response currents of AA and UA to DA were calculated as 6 and 5%, respectively.

Catecholamines↗
PubMed2005

Dynamic characteristics of carotid sinus pressure-nerve activity transduction in rabbits.

The dynamic characteristics of the baroreflex neural arc from pressure input to efferent sympathetic nerve activity (SNA) reveal derivative characteristics in the frequency range of 0.01 to 0.8 Hz (i.e., the baroreflex gain augments with increasing frequency) and high-cut characteristics in the frequency range above 0.8 Hz (i.e., the baroreflex gain decreases with increasing frequency) in rabbits. The derivative characteristics accelerate the arterial pressure regulation via the baroreflex. The high-cut characteristics preserve the baroreflex gain against pulsatile pressure by attenuating the high-frequency components less necessary for arterial pressure regulation. However, to what extent the carotid sinus baroreceptor transduction from pressure input to afferent baroreceptor nerve activity (BNA) contributes to these characteristics remains unanswered. To test the hypothesis that the carotid sinus pressure-BNA transduction partly explains the derivative characteristics but not the highcut characteristics, we examined the dynamic BNA response to pressure input in the frequency range from 0.01 to 3 Hz by using a white noise analysis in 7 anesthetized rabbits. The transfer function from pressure input to BNA showed slight derivative characteristics in the frequency range from 0.01 to 0.3 Hz with approximately a 1.7-fold increase in dynamic gain, but it showed no high-cut characteristics. In conclusion, the carotid sinus baroreceptor transduction partly explained the derivative characteristics but not the high-cut characteristics of the baroreflex neural arc. The present results suggest the importance of the central processing from BNA to efferent SNA to account for the overall dynamic characteristics of the baroreflex neural arc.

Animals↗
PubMed2005

Dynamic and static baroreflex control of muscle sympathetic nerve activity (SNA) parallels that of renal and cardiac SNA during physiological change in pressure.

Despite accumulated knowledge on human baroreflex control of muscle sympathetic nerve activity (SNA), whether baroreflex control of muscle SNA parallels that of other SNAs, in particular renal and cardiac SNAs, remains unclear. Using urethane and alpha-chloralose-anesthetized, vagotomized and aortic-denervated rabbits (n = 10), we recorded muscle SNA from tibial nerve by microneurography, simultaneously with renal and cardiac SNAs by wire electrode. To produce a baroreflex open-loop condition, we isolated the carotid sinuses from systemic circulation and altered the intracarotid sinus pressure (CSP) according to a binary white noise sequence of operating pressure +/- 20 mmHg (for investigating dynamic characteristics of baroreflex) or in stepwise 20-mmHg increments from 40 to 160 mmHg (for investigating static characteristics of baroreflex). Dynamic high-pass characteristics of baroreflex control of muscle SNA, assessed by the increasing slope of transfer gain, showed that more rapid change of arterial pressure resulted in greater response of muscle SNA to pressure change and that these characteristics were similar to cardiac SNA but greater than renal SNA. However, numerical simulation based on the transfer function shows that the differences in dynamic baroreflex control at various organs result in detectable differences among SNAs only when CSP changes at unphysiologically high rates (i.e., 5 mmHg/s). On the other hand, static reverse-sigmoid characteristics of baroreflex control of muscle SNA agreed well with those of renal or cardiac SNAs. In conclusion, dynamic-linear and static-nonlinear baroreflex control of muscle SNA is similar to that of renal and cardiac SNAs under physiological pressure change.

Animals↗
PubMed2005

Overexpression of mitochondrial transcription factor a ameliorates mitochondrial deficiencies and cardiac failure after myocardial infarction.

BACKGROUND: Mitochondrial DNA (mtDNA) copy number is decreased not only in mtDNA-mutation diseases but also in a wide variety of acquired degenerative and ischemic diseases. Mitochondrial transcription factor A (TFAM) is essential for mtDNA transcription and replication. Myocardial mtDNA copy number and TFAM expression both decreased in cardiac failure. However, the functional significance of TFAM has not been established in this disease state. METHODS AND RESULTS: We have now addressed this question by creating transgenic (Tg) mice that overexpress human TFAM gene and examined whether TFAM could protect the heart from mtDNA deficiencies and attenuate left ventricular (LV) remodeling and failure after myocardial infarction (MI) created by ligating the left coronary artery. TFAM overexpression could ameliorate the decrease in mtDNA copy number and mitochondrial complex enzyme activities in post-MI hearts. Survival rate during 4 weeks of MI was significantly higher in Tg-MI than in wild-type (WT) littermates (WT-MI), although infarct size was comparable. LV cavity dilatation and dysfunction were significantly attenuated in Tg-MI. LV end-diastolic pressure was increased in WT-MI, and it was also reduced in Tg-MI. Improvement of LV function in Tg-MI was accompanied by a decrease in myocyte hypertrophy, apoptosis, and interstitial fibrosis as well as oxidative stress in the noninfarcted LV. CONCLUSIONS: Overexpression of TFAM inhibited LV remodeling after MI. TFAM may provide a novel therapeutic strategy of cardiac failure.

Animals↗
PubMed2005

Overexpression of eNOS in brain stem reduces enhanced sympathetic drive in mice with myocardial infarction.

Reduced nitric oxide (NO) in the brain might contribute to enhanced sympathetic drive in heart failure (HF). The aim of this study was to determine whether increased NO production induced by local overexpression of endothelial NO synthase (eNOS) in the nucleus tractus solitarius (NTS) of the brain stem reduces the enhanced sympathetic drive in mice with HF. Myocardial infarction (MI) was induced in mice by ligating the left coronary artery. MI mice exhibited left ventricular dilatation and a reduced left ventricular ejection fraction. Urinary norepinephrine excretion in MI mice was greater than that in sham-operated mice, indicating that sympathetic drive was enhanced in this model. Thus this model has features that are typical of HF. Western blot analysis and immunohistochemical staining for neuronal NOS (nNOS) indicated that nNOS protein expression was significantly reduced in the brain stem of MI mice. MI mice had a significantly smaller increase in blood pressure evoked by intracisternal injection of N(G)-monomethyl-L-arginine than sham-operated mice. Adenoviral vectors encoding either eNOS (AdeNOS) or beta-galactosidase (Adbeta gal) were transfected into the NTS to examine the effect of increased NO production in the NTS on the enhanced sympathetic drive in HF. After the gene transfer, urinary norepinephrine excretion was reduced in AdeNOS-transfected MI mice but not in Adbeta gal-transfected MI mice. These results indicate that nNOS expression in the brain stem, especially in the NTS, is reduced in the MI mouse model of HF, and increased NO production induced by overexpression of eNOS in the NTS attenuates the enhanced sympathetic drive in this model.

Adenoviridae↗
PubMed2005

Muscle sympathetic nerve activity averaged over 1 minute parallels renal and cardiac sympathetic nerve activity in response to a forced baroreceptor pressure change.

BACKGROUND: Despite the accumulated knowledge of human muscle sympathetic nerve activity (SNA) as measured by microneurography, whether muscle SNA parallels renal and cardiac SNAs remains unknown. METHOD AND RESULTS: In experiment 1, muscle (microneurography, tibial nerve), renal, and cardiac SNAs were recorded in anesthetized rabbits (n=6) while arterial pressure was changed by intravenous bolus injections of nitroprusside (3 microg/kg) followed by phenylephrine (3 microg/kg). In experiment 2, the carotid sinus region was vascularly isolated in anesthetized, vagotomized, and aorta-denervated rabbits (n=10). The 3 SNAs were recorded while intracarotid sinus pressure was increased stepwise from 40 to 160 mm Hg in 20-mm Hg increments maintained for 60 seconds each. Muscle SNA averaged over 1 minute was well correlated with renal (r=0.96+/-0.01, mean+/-SE) and cardiac (r=0.96+/-0.01) SNAs in experiment 1 (baroreflex closed-loop condition) and also with renal (r=0.97+/-0.01) and cardiac (r=0.97+/-0.01) SNAs in experiment 2 (baroreflex open-loop condition). CONCLUSIONS: Muscle SNA averaged over 1 minute parallels renal and cardiac SNAs in response to a forced baroreceptor pressure change.

Animals↗