Local Hemodynamic Changes in Hypertension

Abstract

Abstract-As a result of antihypertensive therapy, there has been a remarkable decrease in morbidity and mortality from such cardiovascular endpoints as stroke, coronary heart disease, and major hypertensive emergencies. In contrast, there has been no relenting in the increasing prevalence of cardiac failure and end-stage renal disease (ESRD) associated with hypertensive cardiovascular disease. Recent experience in our laboratories that involved the natural development of the cardiac and renal hemodynamic alterations in spontaneously hypertensive rats demonstrated that the natural history and pathophysiological lesions associated with cardiac failure and ESRD may be vastly different from the heretofore more pressure-dependent brain and other cardiac endpoints reported in earlier years. These initial antihypertensive agents (eg, diuretics, ␤-adrenergic receptor inhibitors) had minimal anti-ischemic and antifibrotic effects on heart and kidney and did not exert the cardiac and nephroprotective hemodynamic effects of the newer classes of agents. The cardiac and renal endpoints resulting in organ failure today are more related to ischemia, intraorgan fibrosis, and aging. Our experimental studies summarized herein strongly suggest that the newer classes of antihypertensive drugs (ie, ACE inhibitors, angiotensin II type 1 receptor antagonists, certain calcium antagonists, and perhaps L-arginine) may reverse these pathophysiological lesions through improving blood flow and flow reserve, their antifibrotic and other actions.

Muscle blood flow and oxygenation measured by NMR imaging and spectroscopy

“…In addition, these hypertensive animals were unable to maintain muscle vasodilatation over prolonged periods of time (95). This new observation might be of importance in explaining the increased sensitivity of target-organs to ischaemia in hypertension (111). There were also some totally unexpected findings.…”

Brain Perfusion and Cognitive Function Changes in Hypertensive Patients

“…These data are in accord with the results of Chazova et al, who observed an improvement in brain perfusion in AH patients after 6 months of treatment with perindopril (6). Moreover, the experimental investigations of Frohlich (25) demonstrated that modern antihypertensive drugs, including ACE inhibitors, were able to reverse the pathophysiological disorders observed in hypertension by improving the circulation and vascular reserve. Although there is no direct evidence that hypotensive therapy has a positive effect on the remodeling of the cerebral arteries in hypertensive patients, some investigations have shown that antihypertensive drugs, especially ACE inhibitors, are able to regress the media hypertrophy of peripheral arteries and increase their luminal diameter (18).…”

Role of 20-Hydroxyeicosatetraenoic and Epoxyeicosatrienoic Acids in the Regulation of Vascular Function in a Model of Hypertension and Endothelial Dysfunction

“…In this model of endothelial dysfunction and severe hypertension (SHR/ L -NAME), prolonged inhibition of nitric oxide synthase produces oxidative stress and inflammatory changes accompanied any morphological and functional changes such as abnormal vascular reactivity, marked proteinuria, nephrosclerosis as well as cardiac dysfunction, all pathological conditions that are consistent with what may be found in clinical hypertensive disease [10][11][12][13][14] .…”