Endothelium-dependent relaxation in pulmonary arteries of L-NAME-treated Wistar and stroke-prone spontaneously hypertensive rats.

Sekiguchi F, Yamamoto K, Matsuda K, Kawata K, Negishi M, Shinomiya K, Shimamur K, Sunano S.

Department of Anatomy and Physiology, Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka, 577-8502, Japan. fumiko phar.kindai.ac.jp

To evaluate whether the elevated blood pressure induced by chronic treatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) contributes to an impairment of endothelium-dependent relaxation (EDR), the effects of chronic treatment of Wistar rats with L-NAME on systolic blood pressure, pulmonary arterial blood pressure and EDR of the pulmonary arteries were studied and compared with those of stroke-prone spontaneously hypertensive rats (SHRSP). While the systolic blood pressure (SBP) of Wistar rats was increased above that of controls by chronic treatment with L-NAME, it was still significantly lower than that of SHRSP. Chronic treatment with L-NAME did not affect pulmonary arterial blood pressure. On the other hand, the pulmonary arterial blood pressure of SHRSP was slightly but significantly higher than that of the control normotensive Wistar Kyoto rats (WKY). EDR in response to acetylcholine in the pulmonary artery of L-NAME-treated rats was significantly smaller than that in control Wistar rats. The EDR markedly increased in the presence of L-arginine and completely disappeared in the presence of N(omega)-nitro-L-arginine. Indomethacin hardly affected EDR. In preparations from SHRSP, the EDR was not different from that in those from WKY. Relaxation induced by sodium nitroprusside was identical in all preparations. Elevation of SBP and the impairment of EDR observed in L-NAME-treated rats recovered two weeks following cessation of treatment. These results suggest that the impaired EDR in the pulmonary artery of L-NAME-treated rats is not due to an L-NAME-induced increase in blood pressure but due to the inhibition of nitric oxide synthase by the drug remaining in the endothelium.

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A relation between blood pressure and stiffness of joints and skin.

Uiterwaal CS, Grobbee DE, Sakkers RJ, Helders PJ, Bank RA, Engelbert RH.

Julius Center for Health Sciences and Primary Care, University Medical Center, Wilhelmina Children's Hospital, Ulrecht, The Netherlands. c.s.p.m.uiterwaal jc.azu.nl

BACKGROUND: Blood pressure, particularly pulse pressure, is associated with arterial wall stiffness, but little is known about its relation to stiffness of other parts of the body. We examined the extent to which blood pressure levels in young healthy children are related to stiffness of various tissues. METHODS: In November 2000, we studied 95 healthy prepubertal children (41 boys and 54 girls, within age range 8-10 years) from two primary schools in the city of Zeist, The Netherlands. Systolic and diastolic blood pressure and pulse pressure were analyzed in relation to various tissue indicators of stiffness, including active joint mobility and skin extensibility. All results were adjusted for age, sex, body height, body weight and muscle strength as possible confounders. RESULTS: Diastolic blood pressure was lower with increased active joint mobility (multivariate generalized linear regression coefficient = -4.5 mmHg per standard deviation [SD] joint mobility; 95% confidence interval [CI] = -7.8 to -1.2). Pulse pressure was lower with increased skin extensibility (-3.2 mmHg per SD skin extensibility; CI = -5.2 to -1.1), through a higher diastolic blood pressure (2.0 mmHg per SD skin extensibility; CI = 0.2-3.9) and possibly lower systolic blood pressure (-0.8 mmHg per SD skin extensibility; CI = -3.5 to 1.9). These associations were mutually independent. Additional adjustment for reported musculoskeletal problems or physical activity levels did not materially change the findings. CONCLUSIONS: Our findings support the hypothesis that constitutional stiffness of body tissues may be associated with blood pressure levels and eventually cardiovascular risk.

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[Correlation of anthropometric parameters and blood-pressure in elderly people]

[Article in Hungarian]

Rurik I, Nagy K, Antal M.

Vorosmarty utcai (XX. ker.) Haziorvosi Rendelo, Budapest. rurik.dr axelero.hu

INTRODUCTION: The elderly represent a growing segment of populations in developed and also in developing countries. Anthropological measurements offer a cheap and easy way method for assessment of health and nutritional status and in prediction for mortality. Anthropological parameters and their relation to blood pressure were studied in elderlies. METHODS: Two hundred-thirteen elderly people (83 men over 65 y and 110 women over 60 y) were involved. The weight, height, waist- and hip circumferences were measured and waist: hip ratio, and body mass index (BMI) were calculated. Blood pressure was measured by the use of sphygmomanometer. Hypertension was diagnosed when systolic blood pressure was >/= 140 and/or diastolic >/= 90 mmHg. The SPSS 10 version for Windows was used for statistical analysis. RESULTS: According to the BMI, 72% of men and 65% women were considered overweight or obese. According to waist circumference 51% of men and 83% of women belonged to the high risk group. Under 80 y the mean blood pressure was in the pathological range both in the case of men and women. That could be considered as a sign of the insufficient efficiency of treatment or bad compliance. By 60% of this elderly population hypertension was registered. 75% of people, considered overweight or obese according to BMI, showed hypertension. According to the waist circumference, in 73% of people in the high risk group hypertension was detected versus 6% of persons in the non-risk group. This relation could not be observed in women. CONCLUSION: The prevalence of obesity and overweight is higher in the elderly group than in the younger adult population. Decrease in body mass may be suggested only by cautious nutritional intervention, control of systolic blood pressure should be more regular and prudent.

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Blood lead level is associated with elevated blood pressure in blacks.

Vupputuri S, He J, Muntner P, Bazzano LA, Whelton PK, Batuman V.

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Chronic lead exposure has been associated with elevated blood pressure in epidemiological studies. It is not known whether the previously observed relation between blood lead and hypertension persists after significant reductions have been made in environmental lead contamination. We examined the relation between blood lead levels and blood pressure in a representative sample of 14 952 whites and blacks aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey. Blood lead was measured by atomic absorption spectrophotometry and blood pressure by standard sphygmomanometry. Mean blood lead levels were significantly higher for black men and women (5.4 and 3.4 microg/dL, respectively) compared with white men and women (4.4 and 3.0 microg/dL, respectively). After multivariate adjustment for important covariables, each standard deviation higher blood lead (3.3 microg/dL) was associated with a 0.82 (95% confidence interval [CI], 0.19 to 1.44) mm Hg and a 1.55 (95% CI, 0.47 to 2.64) mm Hg higher systolic blood pressure among black men and women, respectively. In contrast, blood lead level was not associated with blood pressure among white men or women. The multivariate-adjusted odds ratio (95% CI) of hypertension associated with a 1-SD higher level of blood lead was 1.08 (95% CI, 0.99 to 1.19) for black men and 1.39 (95% CI, 1.21 to 1.61) for black women. These findings suggest that increased levels of blood lead remain an important environmental risk factor for elevated blood pressure in blacks.

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Contrasting regression of blood pressure and cardiovascular structure in declipped renovascular hypertensive rats.

Kvist S, Mulvany MJ.

Department of Pharmacology, Bartholin Building, University of Aarhus, 8000 Aarhus C, Denmark. stinne.kvist dadlnet.dk

We investigated the time relationship between changes in blood pressure and changes in the structure of the resistance vasculature. Blood pressure, heart/body weight ratio, and morphology and function of mesenteric resistance arteries from 1-kidney, 1-clip renovascular hypertensive rats were followed before and after declipping at age 14 weeks. The rats were divided into 5 groups, which were investigated 6 hours, 24 hours, 1 week, 4 weeks, and 8 weeks after declipping and compared with 2 normotensive and 2 renovascular hypertensive control groups at 14 weeks and 18 weeks. Systolic blood pressure was elevated 2 weeks after application of the clip and stabilized after 6 weeks. Declipping induced a prompt fall in blood pressure within 6 hours, and blood pressure was normalized within 1 week. Heart/body weight ratio was increased in renovascular hypertensive rats, and declipping induced a gradual decrease in the ratio, which was normalized within 4 weeks. Media/lumen ratio and media area of mesenteric resistance arteries were increased in renovascular hypertensive rats, and declipping did not affect media/lumen ratio and media area within 8 weeks, although there was a tendency for some regression of media/lumen ratio. There were no differences in response to high potassium, noradrenaline, or acetylcholine. Thus, these findings show definitively that declipping causes rapid reversal of renovascular hypertension in rats accompanied by gradual reduction of the heart/body weight ratio but lack of normalization in the mesenteric resistance vessels. This provides clear evidence that neither vascular nor cardiac structural changes are capable of keeping rats hypertensive.

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Gender differences in ET and NOS systems in ETB receptor-deficient rats: effect of a high salt diet.

Taylor TA, Gariepy CE, Pollock DM, Pollock JS.

Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USA.

The purpose of this study was to determine if rats lacking the ETB receptor have altered renal endothelin (ET) production and NO synthase (NOS) activity in response to high salt and if female rats are better able to control blood pressure through higher NOS activity in rats heterozygous (sl/+) and homozygous (sl/sl) for ETB receptor deficiency. On normal salt (0.4% NaCl; NS), male sl/sl rats had higher systolic blood pressures compared with male sl/+ and female sl/+ and sl/sl rats. On a high salt diet (10% NaCl; HS), blood pressure in male sl/+ rats was significantly higher than female sl/+ rats. However, ETB receptor deficiency caused much larger increases in blood pressure in male and female rats. On NS, urinary ET excretion was not different between male and female of either genotype. HS significantly increased ET excretion in male and female sl/+ rats, but the increase was significantly less in sl/sl compared with sl/+. Homogenates of inner medullary collecting duct tissue were separated into particulate and cytosolic fractions and total NOS activity measured by conversion of [3H]L-arginine to [3H]L-citrulline. Female rats had significantly greater cytosolic NOS activity compared with male rats on NS. On HS, cytosolic NOS activity was lower in all groups compared with NS rats, whereas particulate NOS activity was significantly greater in male and female sl/+ rats compared with male and female sl/sl rats. These data support our hypothesis that NOS protects against rises in blood pressure in female rats and ETB receptors prevent further increases in blood pressure due to increases in renal ET production and NOS activity.

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Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A1 and A2A subtype receptor agonists.

Schindler CW, Karcz-Kubicha M, Thorndike EB, Muller CE, Tella SR, Ferre S, Goldberg SR.

Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Department of Health and Human Services, National Institutes of Health/National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA. cschindl helix.nih.gov

1. The cardiovascular effects of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the adenosine A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) were investigated in rats implanted with telemetry transmitters for the measurement of blood pressure and heart rate. 2. Intraperitoneal (i.p.) injections of the adenosine A1 receptor agonist CPA led to dose-dependent decreases in both blood pressure and heart rate. These effects of 0.3 mg kg(-1) CPA were antagonized by i.p. injections of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethyl-xanthine (CPT), but not by i.p. injections of the adenosine A2A receptor antagonist 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-methyl-1-propargylxanthine phosphate disodium salt (MSX-3). Injections (i.p.) of the peripherally acting nonselective adenosine antagonist 8-sulfophenyltheophylline (8-SPT) and the purported nonselective adenosine antagonist caffeine also antagonized the cardiovascular effects of CPA. 3. The adenosine A2A agonist CGS 21680 given i.p. produced a dose-dependent decrease in blood pressure and an increase in heart rate. These effects of 0.5 mg kg(-1) CGS 21680 were antagonized by i.p. injections of the adenosine A2A receptor antagonist MSX-3, but not by i.p. injections of the antagonists CPT, 8-SPT or caffeine. 4. Central administration (intracerebral ventricular) of CGS 21680 produced an increase in heart rate, but no change in blood pressure. MSX-3 given i.p. antagonized the effects of the central injection of CGS 21680. 5. These results suggest that adenosine A1 receptor agonists produce decreases in blood pressure and heart rate that are mediated by A1 receptors in the periphery, with little or no contribution of central adenosine A1 receptors to those effects. 6. The heart rate increasing effect of adenosine A2A agonists appears to be mediated by adenosine A2A receptors in the central nervous system. The blood pressure decreasing effect of adenosine A2A agonists is most probably mediated in the periphery.

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Systemic blood pressure and stroke outcome and recurrence.

Hillis AE.

Department of Neurology, Johns Hopkins Hospital, 600 North Wolfe Street, Meyer 5-185, Baltimore, MD 21287, USA. argye jhmi.edu

Although it is clear that hypertension is a primary cause of stroke, there has been controversy concerning blood pressure management after stroke. Recent studies indicate that lowering systemic blood pressure after stroke reduces the risk for recurrent stroke or vascular events, but other studies provide evidence that blood pressure should not be lowered in the first week after stroke onset. Additional investigations have provided preliminary evidence that raising blood pressure in the first few days after stroke may improve outcome in selected patients. However, other studies have recorded the benefit of lowering blood pressure in some patients at the acute stage, whereas still others have identified patients in whom lowering blood pressure even later after stroke may be more harmful than beneficial. The remaining challenge is to identify efficient measures for determining when to lower blood pressure in each case of ischemic stroke.

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