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Abstract-Ghrelin is an orexigenic peptide originally isolated from the stomach. Intravenous administration of ghrelin has been shown to elicit a decrease in arterial pressure without a significant change in heart rate (HR), suggesting that ghrelin may act on the central nervous system to modulate sympathetic activity. The aim of the present study was to determine the central effects of ghrelin on cardiovascular and sympathetic responses in conscious rabbits. Key Words: baroreceptors Ⅲ blood pressure Ⅲ central nervous system Ⅲ ghrelin Ⅲ nervous system, sympathetic renal G hrelin, an acylated 28-residue peptide originally isolated from the rat stomach, is an endogenous ligand for the growth hormone (GH) secretagogue receptor. 1,2 Although ghrelin is likely to regulate pituitary GH secretion along with GH-releasing hormone and somatostatin, 2,3 GH secretagogue receptors have also been identified in hypothalamic neurons and in the brainstem. 4,5 Intracerebroventricular (ICV) administration of ghrelin has been shown to generate a dose-dependent increase in food intake and body weight, 6,7 suggesting that ghrelin participates in the regulation of food intake and GH secretion. Furthermore, ICV administration of ghrelin has been shown to increase plasma vasopressin level without a significant change in arterial pressure in conscious rats. 8 It has also been reported that intravenous injection of human ghrelin elicits a decrease in blood pressure without an increase in heart rate (HR) in healthy men. 9 In addition, plasma ghrelin concentration is increased in patients with cachexia associated with chronic heart failure. 10 These previous findings suggest that ghrelin may participate not only in feeding behavior but also in cardiovascular and sympathetic regulation. Although ghrelin has been reported to have a vasodilatory effect in humans, 11 the underlying mechanisms of depressor response induced by intravenous injection of ghrelin have not yet been determined. Because the depressor response was not accompanied by tachycardia, it is likely that mechanisms other than direct vasodilating effects, at least in part, are involved in this depressor response. To clarify the mechanisms for this depressor response, the effects of ghrelin on sympathetic activity and on the baroreceptor reflex should be determined. We hypothesized that intravenous administration of ghrelin acts at the central nervous system to modulate the sympathetic nervous system, resulting in a decrease in arterial pressure without tachycardia. Accordingly, in the present study, we focused on the central effect of ghrelin on sympathetic activity and baroreceptor reflex. To evaluate the sympathetic nervous system precisely, the present study was conducted on conscious rabbits with direct recording of renal sympathetic nerve activity (RSNA), because the sympathetic nervous system and baroreceptor reflex are greatly affected by anesthesia. 12,13

INTRODUCTIONSince Riva-Rocci invented indirect brachial cuff sphygmomanometry in 1896 1 and Korotkoff proposed the auscultatory method in 1905, 2 the method for blood pressure (BP) measurements has remained essentially unchanged for the past 100 years.In 1969, Posey et al. 3 identified mean BP on the basis of the cuff-oscillometric method. With subsequent theoretical and technical improvements, the method to determine systolic and diastolic BP (S and D, respectively) was introduced to the cuff-oscillometric method. As a result, many of the automatic electronic sphygmomanometers available today have adopted this method, and those different from the auscultatory method have begun to be used in general clinical practice. Since the advent of indirect methods for sphygmomanometry, the past century has developed the practical and clinical sciences of hypertension. However, BP information necessary for the diagnosis and treatment of hypertension is still obtained essentially on the basis of casual measurements at the outpatient clinic (clinic BP). However, the reliability of clinic BP was called into question 40 years after the advent of indirect sphygmomanometry. In 1940, Ayman and Goldshine 4 widely adopted the concept of self-BP measurements in the field of clinic BP measurements and demonstrated discrepancies between clinic BP and self-BP measurements. Bevan, 5 in the United Kingdom, first reported the results of ambulatory BP (ABP) monitoring (ABPM) using a direct arterial BP measurement method in 1969, and showed that human BP changes markedly with time. The quantity and quality of BP information vary greatly according to different methods, and the problem of interpreting clinic BP, which is obtained specifically in a medical environment, has been an issue in the clinical practice of hypertension during the past 50 years.However, the practice and epidemiology of hypertension still depend entirely on BP information obtained in a medical environment (clinic BP/BP at a health examination), resulting in the

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Background: It is not known whether the treatment recommendations presented in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure are applicable to the Japanese elderly population. Methods: We followed up 588 cardiovascular diseasefree residents of a Japanese community who were 60 years or older from November 1, 1961, through October 31, 1993. Treated hypertensive patients were excluded from the analysis. During this period, CVD occurred in 179 subjects. The incidences were estimated by the pooling of repeated observations method. Results: The age-and sex-adjusted incidences of cardiovascular disease significantly increased with elevated blood pressure levels. The hazard ratio for stage 3 hypertension was 5.34 (95% confidence interval, 2.66-10.71; P<.001) compared with optimal blood pressure after adjustment for other covariates. Among subjects aged 60 to 79 years, the incidences for stages 1 through 3 hy-pertension were significantly higher than for those with optimal and normal blood pressure. In comparison, among those 80 years or older, the incidence was significantly higher only in patients with stage 3 hypertension. We further estimated the incidences according to the risk stratification system. In the younger elderly subjects, the incidences increased with rising blood pressure levels in each risk stratum. Similar relationships were not observed among the older elderly subjects. Conclusions: Our findings demonstrate that the recommendations of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure were potentially applicable to the Japanese elderly subjects 79 years or younger. Based on our findings, however, hypertension might not be a risk factor for cardiovascular disease among very old hypertensive patients with advanced atherosclerosis.