Models of steroid-induced hypertension in man and rat have been well characterized but the mechanisms by which ACTH and glucocorticoids raise blood pressure are not fully understood. Recently described paracrine (eg endothelial nitric oxide) and humoral (eg PHF) factors may be important in human essential hypertension. These factors were examined in cortisol-induced hypertension in man and ACTH-induced hypertension in the rat respectively. In man, the haemodynamic effects of ACTH can be attributed to the adrenal production of cortisol, but whether the major rodent glucocorticoid corticosterone is responsible for ACTH-induced hypertension in the rat has not been resolved. This question was examined in these studies. In male volunteers, exogenous cortisol raised blood pressure and suppressed endothelium-dependent vasodilatation, by a mechanism which may be nitric oxide synthase dependent. Although dexamethasone and fludrocortisone also raised blood pressure, attenuation of cholinergic vasodilatation was not observed. From these studies, the data suggest that the effect of cortisol on endothelium-dependent vasodilatation is unique to the endogenous hormone and not reproduced by synthetic agonists of GR or MR. Impaired endothelial vasodilator function may contribute to cortisol-induced hypertension in man. In the rat, exogenous corticosterone, administered in doses to achieve circulating concentrations similar to those observed in the experimental model of ACTH excess, reproduced the haemodynamic and some of the metabolic changes which characterize ACTH-induced hypertension. Further, like ACTH-induced hypertension, corticosterone-induced hypertension was prevented by L- but not D-arginine, and this effect was completely prevented by NOLA. It is likely that adrenal corticosterone mediates the hypertensive effects of ACTH excess. Parathyroidectomy had no significant effect on the rise in blood pressure secondary to ACTH excess. It is unlikely that PHF contributes to the model of ACTH-induced hypertension in the rat. The bioassay for the measurement of PHF could not be reproduced in our laboratory, leaving a question mark about the relevance of this putative factor in hypertension research.

Faculty of Health Sciencs School of physiology 0010633J bnkeh@uycdc.uninet.m / Blood pressure (BP) is a heritable trait. However, the loci responsible and the mechanisms by which these genes determine BP are uncertain. Based on widely published data regarding frequent phenotypic characteristics that exemplify essential hypertension (EHT) in persons of African ancestry, in the present thesis I explored the role of gene candidates most likely to contribute to BP in this group. In this regard a high frequency of persons of African descent experience increases in BP in response to an enhanced salt intake (salt-sensitive hypertension). In addition, many patients of African origin with EHT fail to respond to inhibition of angiotensin-converting enzyme (ACE) with an appropriate decrease in BP, a factor that cannot be explained entirely on the basis of reduced plasma renin levels in this group. Thus, I evaluated the role of several gene variants that could influence either renal salt handling or the activity and effects of the renin-angiotensin system on BP in subjects of African ancestry. Although the angiotensinogen (AGT) gene has at least 3 variants in the promoter region that influence angiotensinogen expression and which occur with a remarkably high frequency in populations of African ancestry, their role in this group is still controversial. To-date, interactions between these variants have not been considered. Using a casecontrol study design in a sample of 1325 subjects, as well as association analysis with 24 hour ambulatory BP (ABP) values in 626 hypertensives, I confirmed that an independent effect of functional AGT gene variants on the risk for EHT or 24 hour ABP was weak at best. Importantly, however, interactions between the -20A C and -217G A variants were noted to strongly impact on the risk for EHT as well as ABP. Furthermore, interactions between the -20A C and -217G A variants played a major role in iii contributing toward the variability of ABP responses to ACE inhibitors, but not calcium channel blockers in this population group, with genotype determining whether or not ACE inhibitor responses occurred. Although the 825C T polymorphism of the guanosine triphosphate (G) protein 3 subunit (GNB3) gene influences the activity of a substance that modifies renal salt handling, namely the Na+/H+ exchanger, its impact in hypertensives of African descent is controversial. In the present thesis I confirmed in a large sample that the GNB3 variant was not associated with the risk for EHT or ABP values in subjects of African ancestry. However, because the activity of the exchanger is enhanced in obesity I hypothesised that the GNB3 gene variant could mediate a clinically relevant BP effect by modifying the impact of body size on BP (type I or II genetic effect). Indeed, GNB3 genotype proved to be a strong determinant of the impact of body size on systolic BP values, with genotype determining whether or not the effect occurred. The epithelial sodium channel (ENaC) and atrial natriuretic peptide (ANP) have an important influence on renal salt handling. The T594M polymorphism of the -subunit of the ENaC gene only exists with a relatively high frequency in subjects of African ancestry. Previous studies conducted in this population group in relatively small samples have indicated that the ENaC and ANP gene variants determine BP in subjects of African descent. In a larger sample of subjects of African descent I demonstrated that the T594M polymorphism of the ENaC gene has no impact on BP in this population group. However, my results suggest that the ANP gene may be a candidate worthy of further study. In conclusion, the results described in this thesis provide evidence that lends some clarity to the role of likely gene candidates for BP control in people of African descent. iv Importantly, data from this thesis suggest that interactions between functional variants of specific loci (e.g the AGT gene), and clinically relevant type I or II genetic effects (no independent actions, but modifier gene effects, e.g, GNB3) should be considered before excluding loci as playing an important role in BP control. Moreover, this thesis provides the first substantial data to indicate that gene variants determine the variability of BP responses to pharmacological agents in hypertension in this population group.

Title: Analysis of pharmacotherapy and drug related problems in patients with arterial hypertension in Greece Student: Zisis Papadopoulos Tutor: Jiri Vlcek Department of Social and Clinical Pharmacy, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Background: Arterial hypertension or high blood pressure is a chronic medical condition which is characterized by elevated blood pressure in the arteries and is an important risk factor for future development of cardiovascular disease. Also belongs to asymptomatic diseases because it usually does not cause symptoms for years until a vital organ is damaged. Moreover is a major cause of morbidity and mortality, due to its association with some other serious diseases like coronary heart disease, cerebrovascular disease, atherosclerosis, renal disease, dyslipidemia, diabetes, obesity and metabolic syndrome. Arterial hypertension for adults, who don't suffer from any other kind of diseases, is defined by an elevation of blood pressure to 140 / 90 mm Hg or to higher values. Aim: In the theoretical part the main aim is to analyze information regarding etiopathogenesis, diagnostic methods and treatment strategies of arterial hypertension, as well as classification and causes of drug-related-problems to antihypertensive agents. In the...

Th.--Pharm.--Paris 5, 1982. N°: 65.

Introduction Tobacco addiction, obesity, hypertension and physical inactivity are common risk factors of non-communicable diseases. Information on the prevalence of risk factors is needed for inter alia planning of services. Sample A community-based sample of 99 subjects of both genders, aged 20 to 59 years, was randomly selected. Method Smoking status and physical activity levels were determined using a questionnaire. Hypertension (systolic blood pressure >160mmHg / diastolic blood pressure >90mmHg) and obesity (body mass index (8MI) >30kg/m2, waist-hip ratio (WHR) >1(males), >0.84 (females» were measured. Results Of the sample, 25% smoked, 6% were hypertensive, 19%(8MI) and 12%(WHR) were obese, 23% inactive at work and 25% inactive during leisure time. Seventy-eight percent did not participate in sport. Each subject had at least one risk factor. Conclusion Socio-economical, behavioural, psychological and cultural factors appear to influence the prevalence rates. Despite relatively low prevalence rates, high-¬risk groups were identified such as male smokers and obese females. Promoting physical activity by physiotherapists as part of comprehensive intervention programmes appears especially appropriate due to its inter-relationship with other risk factors. Prevention and treatment of risk factors should be a health priority. / Dissertation (MSc (Physiotherapy Management))--University of Pretoria, 2005. / Physiotherapy / unrestricted

La dysfonction endothéliale est un problème majeur au niveau mondial du fait de son implication dans de nombreuses pathologies. Ainsi, la dysfonction endothéliale est considérée comme un facteur pronostique défavorable dans les maladies cardiovasculaires. Les principaux mécanismes impliqués dans la dysfonction endothéliale sont la réduction de la formation et/ou de la biodisponibilité du monoxyde d’azote (NO), et la présence d’un stress oxydant. Le but de ce travail était d’évaluer des traitements phytothérapeutiques pouvant prévenir et/ou améliorer la dysfonction endothéliale. Le criblage de plus de trois cent plantes en fonction de leur capacité à induire une relaxation vasculaire et une inhibition de la NADPH oxydase (données confidentielles) a conduit à s’intéresser à Lindera obtusiloba. Ensuite, la capacité d’un extrait alcoolique de Lindera obtusiloba (LOE) à améliorer in vitro et in vivo la dysfonction endothéliale en activant la eNOS et en réduisant le stress oxydant a été testée. En conclusion, ces travaux indiquent que LOE possède des effets vasoprotecteurs in vitro et in vivo dans plusieurs modèles expérimentaux comme l’hypertension artérielle induite par l’angiotensine II, le diabète de type 2, l’athérosclérose et la thrombose pulmonaire. Ces effets bénéfiques impliquent, au moins en partie, la stimulation de la formation endothéliale du NO, la réduction du stress oxydant vasculaire via l’inhibition de la NADPH oxydase et l’inhibition de l’agrégation plaquettaire. Ainsi, LOE pourrait être un excellent candidat pour la prévention et/ou le traitement phytothérapeutique des maladies cardiovasculaires associées à une dysfonction endothéliale. / Endothelial dysfunction is a major worldwide topic because it is an important component and risk factor of a number of common human diseases. Therefore, endothelial dysfunction is considered a hallmark for vascular diseases, and has also been shown to be predictive of future adverse cardiovascular events. The main characteristic is a reduced NO production and bioavailability, and an increased vascular oxidative stress. The goal of the present research was to find a candidate for cardiovascular protective herbal medicine for the treatment of endothelial dysfunction. Through measurement of changes in isometric tension of porcine coronary artery rings, Lindera obtusiloba was selected amongst three hundred plants. Thereafter, the aim of our research was to determine whether an ethanolic extract of L. obtusiloba stems (LOE) improves endothelial dysfunction via activation of endothelial nitric oxide synthase and reduction of oxidative stress oxidase in vitro and in several animal models of cardiovascular diseases, and, if so, to elucidate the underlying mechanism. Altogether, the present findings indicate that LOE has vasoprotective effects both in vitro and in vivo including the Ang II-induced hypertention in rats, a type 2 diabetic mice model, and an atherosclerotic mice model, and a thromboembolism mice model, which involve its ability to stimulate the formation of NO, to reduce oxidative stress in the arterial wall, and to inhibit platelet aggregation. In conclusion, our studies reveal that LOE might be an interesting candidate as a cardiovascular protective herbal medicine in pathologies with endothelial dysfunction.