Cardiovascular Structural Adaptation; its Role in the Initiation and Maintenance of Primary Hypertension

Folkow, Björn

doi:10.1042/cs055003s

Cited by 286 publications

(236 citation statements)

References 18 publications

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“…According to Folkow (8,9), the increased peripheral resistance in hypertension is associated with structural changes, and the increased vascular reactivity could be explained as resulting from narrowing of the vasculature due to increased media thickness which reduces the luminal diameter of the resistance vessels. However, some observations indicate that other factors are involved in the vascular changes observed in hypertension.…”

Section: Hypertension Vs Increased Peripheral Resistance Vs Abnormalimentioning

confidence: 99%

Calcium handling by vascular myocytes in hypertension

Tostes¹,

Wilde²,

Bendhack³

et al. 1997

Braz J Med Biol Res

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Calcium ions (Ca 2+ ) trigger the contraction of vascular myocytes and the level of free intracellular Ca 2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca 2+ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR) have an increased contractile sensitivity to extracellular Ca 2+ and intracellular Ca 2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca 2+ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1) the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca 2+ channel activity in hypertension; 2) Ca 2+ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3) intracellular Ca 2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca 2+ channel agonists and depolarizing interventions, and 4) using the voltage-clamp technique, the inward Ca 2+ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca 2+ channel function and/or an increase in Ca 2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertension.

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Section: Hypertension Vs Increased Peripheral Resistance Vs Abnormalimentioning

confidence: 99%

Calcium handling by vascular myocytes in hypertension

Tostes¹,

Wilde²,

Bendhack³

et al. 1997

Braz J Med Biol Res

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“…4 - 5 Normally, in chronic hypertension, hypertrophy is associated with the well-known structural changes of the resistance vessels, with narrowing of the lumen and an increase in wall/lumen ratio. 6 " 8 As a result, during constriction, there is greater narrowing of the lumen than in ' 8 Presumably, the reason for the slow redevelopment of hypertension in patients after therapy is stopped is a very gradual redevelopment of the amplifier properties after partial regression of structural changes in both vessels and heart. 3 " 5 This is in accord with findings after long-term treatment in the spontaneously hypertensive rat (SHR) with certain drugs.…”

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confidence: 99%

Enalapril can prevent vascular amplifier development in spontaneously hypertensive rats.

1990

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Three groups of spontaneously hypertensive rats (SHR) were given enalapril (25 mg/kg/day) from 4 to 9 weeks, 4 to 14 weeks, and 14 to 20 weeks of age. The drug was stopped and observations continued for another 16-21 weeks. At selected times, we measured blood pressure, in vitro hindquarter vascular resistance properties, left ventricular weight/body weight ratio, and skeletal muscle vessel norepinephrine kinetics in treated and untreated SHR and in Wistar-Kyoto (WKY) rats. At the end of each treatment period, all cardiovascular variables were close to values of WKY rats and well below those of untreated SHR, and the norepinephrine or fractional rate constant was about 25% below those levels. After enalapril was stopped, blood pressure and left ventricular weight/body weight ratio increased in parallel to levels ranging from 30% to 50% of the normal difference between untreated SHR and WKY rats. However, in SHR treated from 4 to 9 weeks and from 4 to 14 weeks of age, hindquarter resistance properties remained close to WKY rat levels for the entire observation period of 16-21 weeks after treatment, suggesting suppression of the enhanced resistance responses of SHR (amplifier properties). In SHR treated from 14 to 20 weeks of age, suppression of amplifier properties was more transient, and they redeveloped partially 5-6 weeks after cessation of therapy. When enalapril was given up to 14 weeks of age, the long-term suppression of amplifier properties was probably mainly through prevention of smooth muscle hypertrophy in resistance vessels and possibly through other mechanisms (eg., "rarefaction"). After that age, its therapeutic action was similar to that of other antihypertenslve drugs where, after drug withdrawal, there is a slow pressure rise in parallel with redevelopment of vascular and cardiac hypertrophy. (Hypertension 1990;16:252-260)

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“…The present article is meant to give a personal account of how some of these insights were obtained experimen-tally and of my views of how the structural factor relates to the other etiologicaJ determinants of primary hypertension. 1 - 3 However, in this context I want to pay tribute to the many outstanding contributions given to this field of research by colleagues all over the world.…”

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confidence: 99%

"Structural factor" in primary and secondary hypertension.

1990

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The history of research on the "structural factor" in primary hypertension is briefly reviewed, and the gradual realization of its important influence on the hemodynamics of hypertension is outlined, as seen from a "personal angle." Experiences from previous studies of normal vascular function in animals were decisive for our first hemodynamic demonstration concerning the "structural upward resetting" of the systemic resistance vessels in human primary hypertension. Subsequent quantitative studies in rats with primary and secondary hypertension complemented these studies, confirming that the critical structural changes are a rapid increase in precapillary resistance at full dilatation associated with an increase in wall/lumen ratio due mainly to media hypertrophy and occurring in both primary and renal hypertension. Analyses were also performed concerning cardiac, barostat, and venous structural resettings, which are briefly mentioned. In our first studies of human primary hypertension, we suggested that the structural factor might itself be genetically reinforced, and increasing evidence in favor of this view is now accumulating. It is further discussed how antihypertensive therapy should be directed primarily against the structural upward resetting, as dependent on the local pressure and "trophic" influences, and some of our results in rat models are outlined. Finally, as the structural factor at the systemic resistance level also invites positive feedback interactions with functional "pressor" influences, it is, in a way, more difficult to explain why 85-90% of people remain normotensive than how hypertension gradually develops in 10-15% of people. This points to some powerful and durable negative feedbacks, which are still poorly understood, because most so far known barostats are readily reset upward in hypertension. It is here that the Muirhead renomedullary depressor system, and perhaps also the unmyelinated baroreceptor-volume receptor afferents, may be of particular importance. {Hypertension 1990;16:89-101) D uring recent decades, the multifactorial nature of primary essential hypertension has become widely recognized; there are at least three major components that can be discerned.1 -2 Thus, in both humans and animals a porygenetic predisposition (the first component), random in humans but fairly uniform in each of the various rat strains, constitutes the sine qua non element behind the rise in blood pressure. The second component is environmental mechanisms, which interact with these various genetic makeups and are mainly composed of neurohormonal psychosocial influences and dietary factors such as salt intake. 1 -4 Then where does the third component, the "structural factor," fit in and how was its important role in hypertension discovered? As is the case in largely all tissues, structural cardiovascular adaptation is a normal and essentially local response to sustained aver-

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Cardiovascular Structural Adaptation; its Role in the Initiation and Maintenance of Primary Hypertension

Cited by 286 publications

References 18 publications

Calcium handling by vascular myocytes in hypertension

Calcium handling by vascular myocytes in hypertension

Enalapril can prevent vascular amplifier development in spontaneously hypertensive rats.

"Structural factor" in primary and secondary hypertension.

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