Abdominal Obesity Fatty Acids and Neurogenic Hypertension

As noted previously, NEFAs have been linked epidemiologically to hypertension and its genesis. NEFAs have several actions that could contribute to hypertension and help explain the link between the obesity epidemic and increasing prevalence of hypertension (37). Hypertensive patients are more likely to be overweight and obese than normoten-sive individuals. Moreover, when matched for body mass index, hypertensives are more likely to have a centralized fat pattern and a greater amount of...

CGRP is Protective Against Hypertension Induced End Organ Damage

The results described above in Sections 4 and 4.2 demonstrate that the a-CGRP CT deficient mice display a significant increase in basal blood pressure and a significant decrease in basal coronary flow rates. Hypertension-induced end organ damage is one of the most severe and common consequences of chronic increased blood pressure. Because CGRP has such potent biological effects on the heart and kidneys, and in light of several lines of indirect evidence suggesting that CGRP is an endogenous...

Hypertension Induced by NOS Deficit in the Dahl SS

The Dahl salt-sensitive (Dahl SS) rat has a reduced capacity to generate NO in the renal medulla. The mRNA and immunoreactive protein for each of the NOS isoforms is reduced in the outer medulla of Dahl SS rats compared to normotensive Brown Norway (BN) control rats (Fig. 5 29,79,80 ). Consistent with these observations, total NOS enzyme activity was found to be nearly one-third less in the outer medulla of SS rats than in normotensive salt-resistant BN rats (79). Of greatest importance,...

Microalbuminuria and Antihypertensive Medication

Microalbuminuria (urinary albumin excretion 30-300 mg d) clusters with metabolic syndrome, the prevalence being significantly higher among those with than without metabolic syndrome (12.3 vs 4.7 p 0.004) (31). In many patients, microalbuminuria is attributable to diabetic nephropathy. The presence of microalbuminuria demands attention because it is associated with a 50 increase in cardiovascular risk in the general population (32), suggesting that it reflects more widespread vascular damage. Of...

Multiple roles of kallikreinkinin in hypertension cardiovascular and renal disease and stroke

Using strategies of transgenic and somatic gene transfer, as well as protein infusion approaches to achieve a continuous supply of kallikrein-kinin in vivo, we have shown that the KKS plays an important protective role in the development of hypertension in several animal models (Table 1). In addition to blood pressure reduction, kallikrein gene delivery or kallikrein protein infusion improves cardiac, renal and neurological functions, Kallikrein Gene Delivery or Protein Infusion Attenuates...

Intrarenal Ras Components And Locally Formed Angiotensin Peptides

RAS has been portrayed as an endocrine, paracrine, autocrine, and intracrine system (19-21) and thus it has been difficult to delineate the quantitative contributions of sys-temically delivered vs locally formed Ang peptides to the levels existing in any given tissue. Emerging evidence indicates that local formation is of major significance in the regulation of the Ang peptide levels in many organs and tissues (22,23). Various studies have demonstrated the importance of tissue RAS in the brain,...

ET1 and Renal and Cardiac Target Organ Damage in Experimental Hypertension

ET-1 plays a role in renal and cardiac target organ damage in hypertension. ET-1 production is enhanced under conditions of salt loading, and via renal ETB receptor activation, inhibits sodium re-absorption (46). Ang II infusion combined with high salt increases renal ET-1 (47). In Ang Il-infused mice, the dual ETa ETb receptor blocker bosentan partially prevented the activation of the procollagen gene (48). However, Rothermund et al. studied transgenic rats overexpressing the ren2 gene...

Role of cgrp in hypertension

Although CGRP administration can markedly decrease high BP in humans (2,7), it is not clear what role CGRP plays in human hypertension. Data concerning circulating levels of iCGRP in hypertensive humans have been conflicting. These results have been attributed to several factors including the assay itself, heterogenity of the disease, severity and duration of the hypertension, the degree of end organ damage, and the variety of treatment regimens used in these patients. In contrast, a direct...

Tissue kallikrein in hypertension

Tissue kallikrein was first discovered as a hypotensive substance in 1909 by Abelous and Bardier as they showed that intravenous injection of human urine into the anesthetized dog causes a transient reduction of blood pressure (14). This hypotensive substance was later isolated and identified as an enzyme, which was called kallikrein, a Greek synonym for pancreas (15,16). Although pancreas has been shown to be the major site of human tissue kallikrein synthesis (17), urinary kallikrein mainly...

Augmentation Of Intrarenal Agt And Ang Ii In Hypertension

Although increased internalization of Ang II contributes to the increased intrarenal Ang II in the Ang II-infused model of hypertension, the overall Ang II levels are also due to additional Ang II formation as a consequence of enhanced AGT production. In vivo and in vitro studies have shown that Ang II stimulates intrarenal AGT mRNA localized in proximal tubule cells (75,77,146). Several recent studies have focused on long-term changes in the intrarenal AGT formation in Ang II-dependent...

Fatty acids and cardiovascular risk clinical epidemiology

Abdominal obesity is linked to increased non-esterified fatty acid (NEFA) concentrations and turnover that are resistant to suppression by insulin (1,2). Similarly, physical activity and maximal oxygen consumption, a marker of physical fitness, are inversely associated with plasma NEFA concentrations measured as the area under-the-curve during a standard 2-h oral glucose tolerance test (3). Familial combined hyperlipidemia, a relatively common autosomal dominant trait, is associated with high...

Hypertension Induced by Chronic Inhibition of NO Synthesis

Long-term administration of NOS inhibitors by oral or intravenous administration has been demonstrated to result in sustained hypertension in different species such as mice, rats, rabbits, and dogs (2,5,6,15). Common characteristics of this hypertension model are systemic hypertension, renal vasoconstriction, a reduction in glomerular Kf, and sodium retention (32,33,38,61). In addition to the renal effects, which lead to retention of sodium and water, the increase in arterial blood pressure is...

Role of CGRP in LNAMEInduced Hypertension During Pregnancy

Pregnancy Induced Hypertension

The purpose of this series of experiments was to determine the involvement of CGRP in the vascular adaptations that occur in normal pregnancy and its role in hypertensive L-NAME-treated female rats. Yallampalli et al. (27) has demonstrated that the inhibition of NO synthesis with L-NAME in pregnant rats causes hypertension, proteinuria, fetal growth retardation, and increased fetal mortality. The co-administration of CGRP with the L-NAME prevented the gestational, but not the postpartum...

Role of CGRP in Chronic Hypoxic Pulmonary Hypertension

As described previously, CGRP participates in the regulation of regional organ blood flows both under normal physiological conditions and in the pathophysiology of various disease states. For example, in the lung, CGRP plays a critical role in modulating local pulmonary vascular tone. An excellent review describing the role of CGRP and other endogenous lung neuropeptides in the regulation of the pulmonary circulation has been published 28 . Indeed, to the best of our knowledge, the first report...

Intrarenal Levels Of Angiotensin Ii

Angiotensin Hypertension

Interstitial and Tubular Angiotensin II Intrarenal Ang II is not distributed in a homogenous fashion but is compartmentalized in both regional and segmental manners 121 . Earlier studies indicated that medullary Ang II-levels are higher than the cortical levels in normal rats and increase further in Ang II infused hypertensive rats 81 . The combination of high Ang II levels in the medulla coupled with the high density of Ang II receptors suggest that Ang II exerts a major role in...

Severe paroxysmal hypertension

There are some patients with severe paroxysymal hypertension in whom the baroreflex failure, pheochromocytoma, and medullary vascular compression all appear to be absent. Sometimes paroxysmal hypertension is seen in patients with renal artery stenosis, but this can usually be ruled out with standard diagnostic techniques. In other patients, the etiology is less clear, but certainly it is observed in rare conditions such as tumors in the fourth ventricle or in the ancillary structures 26 ,...

Human Breast Cancer Cell Line Mda-ms231

I., O'Shaughnessy, I. M., Stepniakowski, K. T., Kissebah, A. H., and Goodfriend, T. L. 1996 Obesity hypertension is more closely related to impairment of insulin's fatty acid than glucose lowering action. Hypertension 27 2 , 723-728. 2. Jensen, M. D., Haymond, M. W., Rizza, R. A., Cryer, P. E., and Miles, J. M. 1989 Influence of body fat distribution on free fatty acid metabolism in obesity. J. Clin. Investig. 83, 1168-1173. 3. Franks, P. W., Wong, M.-Y., Luan, J.,...

Role in pathophysiology of hypertension and cardiovascular disorders

In response to an increase in atrial distension, ANP is released into the circulation and mediates natriuretic, diuretic, and vasorelaxant effects. High levels of endogenous ANP are thought to compensate the condition of patients with heart failure by reducing preload and afterload. Evidence suggests that a high plasma ANP-BNP level is a prognostic predictor in humans with heart failure 257-259 . Studies with ANP-deficient genetic strains of mice demonstrated that a defect in the ANP synthesis...

ET Antagonists in Essential Hypertension

Because ETB receptors are both vasoconstrictor and vasodilator, and additionally at least in the mouse have a natriuretic effect, there has been ongoing controversy on whether selective ETA or combined ETA ETB receptor blockers would be more efficacious therapeutically in cardiovascular diseases including hypertension. However, there are no clinical trials available comparing an ETA antagonist to a combined ETA ETB blocker. The combined ETa ETb antagonist bosentan 500 mg to 2000 mg d for 4 wk...

ET Antagonists in Heart Failure Renal Failure and Diabetes Mellitus

Although initial studies of heart failure demonstrated beneficial effects of ET blockade both acutely 78 and with bosentan over 14 d with improved systemic and pulmonary hemodynamics 79 , recent studies such as ENABLE demonstrated increased risk of worsening heart failure in patients treated with bosentan 80 . On the other hand, ETa selective antagonists darusentan increased cardiac index after 3 wk of treatment in the HEAT study, although pulmonary capillary wedge pressure, pulmonary arterial...

Baroreflex failure

Perhaps the most dramatic form of neurogenic hypertension is baroreflex failure 6,7 . Baroreflex failure occurs when afferent IX and X cranial nerves are lost 8 . Although unilateral loss occasionally causes altered heart rate regulation 9,10 , it is more typically tolerated from a cardiovascular standpoint. On the other hand, bilateral loss results acutely in an important syndrome of accelerated hypertension 11 and even encephalopathy 12 . Baroreflex failure should be diagnosed when a patient...

Alcohol withdrawal

One of the most dramatic causes of acute and transient sympathetic activation in hypertension seen in ordinary clinical practice is severe alcohol withdrawal. In the most severely affected patients, fivefold elevations of plasma norepinephrine are by no means rare. Such patients typically have tachycardia and sometimes arrhythmias in association with these dramatic blood pressure elevations. In some cases, sympathetic excitation is a first stage in what later becomes delirium tremens. When...

Postural tachycardia syndrome

In discussions of neurogenic hypertension, orthostatic disorders are rarely considered. Many orthostatic disorders are due to nonautonomic mechanisms, and there may sometimes be evidence of excessive sympathetic activation in some of the patients in response to the depressor pathophysiology, whatever it may be 46 . However, in one syndrome orthostatic intolerance or POTS 47 , it is especially important to keep this potential relationship between an orthostatic abnormality and neurogenic...

Ang Iimediated Signaling Pathways

Ip3 And Dag Pathway

The multiple actions of Ang II are mediated via specific, highly complex intracellular signaling pathways, which are stimulated following initial binding of the peptide to its specific receptors. In mammalian cells, Ang II mediates effects via at least two high-affinity plasma membrane receptors, ATi and AT2. Both receptor subtypes have been cloned and pharmacologically characterized 37,38 . Two other Ang II receptors have been described, namely AT3 and AT4. The AT3 receptor is...

Ang ii effects on leukocytes cell adhesion and chemotaxis in the vasculature

Weibel Palade Bodies Lymphatic

A fundamental process in inflammation is extravasation or recruitment of leukocytes from the vascular lumen to the interstitial tissue 9 . This phenomenon involves three basic steps 1 cell rolling, 2 cell adhesion, and 3 transendothelial migration and chemotaxis movement toward chemotactic stimuli Fig. 2 . Adhesion and transendothelial migration of leukocytes into the vessel wall involve sequential interaction of distinct receptors on the surface of leukocytes and endothelial cells. Cellular...