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Cardiovascular hypertrophy and hypertension: causes and consequences
1Baker Medical Research Institute, Melbourne, Victoria, Australia.
Insights
Chronic hypertension involves increased vascular resistance and left ventricular (LV) hypertrophy, impacting blood pressure and organ health. Targeting hypertrophy regression is crucial for preventing organ damage in hypertensive patients.
Area of Science:
- Cardiovascular Physiology
- Hypertension Research
- Vascular Biology
Background:
- Chronic hypertension is characterized by elevated vascular resistance and left ventricular (LV) hypertrophy, particularly in animal models.
- These changes contribute to enhanced hemodynamic performance, maintaining elevated blood pressure and microcirculatory exchange.
- Vascular remodeling, including luminal narrowing without increased medial mass, can result from non-uniform wall stress distribution.
Purpose of the Study:
- To explore the mechanisms underlying elevated blood pressure and structural changes in chronic hypertension.
- To investigate the roles of angiotensin II, sympathetic nervous system, and angiotensin-converting enzyme (ACE) in hypertension development.
- To assess the potential benefits of targeting cardiovascular hypertrophy regression in human hypertension therapy.
Main Methods:
- Analysis of hemodynamic changes and vascular remodeling in hypertensive models (e.g., Goldblatt hypertension, Spontaneously Hypertensive Rats - SHR).
- Investigation of the effects of interventions like neonatal sympathectomy, prazosin treatment, and ACE inhibitors.
- Examination of the impact of antihypertensive drugs on cardiovascular hypertrophy regression in human hypertension.
Main Results:
- Goldblatt hypertension involves renal artery stenosis resistance, angiotensin II (AngII) effects, and later, cardiovascular amplifier roles.
- Sympathetic nervous system activity is critical for BP elevation and structural changes in SHR; sympathectomy prevents these.
- ACE plays a similar role in cardiovascular development in SHR and WKY rats; ACE inhibitors attenuate hypertension long-term in SHR.
Conclusions:
- Therapeutic strategies aimed at regressing cardiovascular hypertrophy are valuable in managing human hypertension.
- Hypertrophy regression can mitigate non-uniform capillary blood flow distribution, reducing the risk of rarefaction and organ damage.
- Understanding the complex interplay of vascular resistance, hypertrophy, and neurohormonal factors is key to effective hypertension management.
Abstract:
In chronic hypertension, vascular resistance is raised and there is concentric left ventricular (LV) hypertrophy, at least in animal models. Together these changes enhance hemodynamic performance ("amplifier" properties) and help maintain elevated blood pressure (BP) and net microcirculatory exchange. Sometimes there is vascular "remodelling", with only luminal narrowing, but no net increase in medial mass. This can be related to non-uniform distribution of wall stress: when the amount of hypertrophy normalizes average wall stress, that on luminal side tends to be undercorrected accounting for preferential growth in that direction, whilst stress on the adventitial side is overcorrected, which results in a tendency to reabsorb material. In Goldblatt hypertension, about 20% of the rise in BP is due to the renal artery stenosis resistance, with the rest differing during the early and late phases: the early contribution is due to angiotensin II (AngII)-mediated systemic constriction and subtle fluid volume changes, whilst later on the cardiovascular amplifiers take over many of the actions of AngII. In SHR, trophic sympathetic nervous system actions are crucial for the rise in BP and development of structural changes and both contribute to the elevation of BP. Neonatal sympathectomy + prazosin treatment prevents hypertension and structural changes in SHR. Angiotensin converting enzyme (ACE) plays a similar role in cardiovascular development in SHR and Wistar Kyoto (WKY) rats. Prolonged administration of ACE inhibitors to SHR produces long term attenuation of hypertension because of an impaired capacity for cardiovascular development in adult animals. In human hypertension, long term treatment with common antihypertensive drugs is required to produce substantial regression of cardiovascular hypertrophy. Since it imposes marked non-uniformity on the distribution of capillary blood flow, with the potential for rarefaction and organ damage, therapy aimed at regression of hypertrophy is a worthwhile target.