Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
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From the perspective of health care, it is now recognised that approximately 20% of adult population from acculturated societies develop a degree of high blood pressure which is associated with an increased risk of cerebrovascular and coronary artery disease. Some years ago it was recognised that the majority of these individuals would be labelled as having idiopathic or essential hypertension. It was only a small number who would actually be discovered to have a secondary cause. This picture is changing: the identification of single gene disorders of diseases such as polycystic kidney disease which are associated with hypertension is being joined by further research on fundamental mechanisms which may explain other clusters of the disorder. However, what seems clear is that ultimately whatever the stimulus, eventually the same haemodynamic alterations by and large underlie the rise in blood pressure. Therefore, when it has become established, there is evidence of an increase in peripheral vascular resistance.

In consequence, much recent research has focused upon first, what constitutes a blood vessel that contributes to peripheral vascular resistance and second, what changes occur in such blood vessels when pressure has risen?

Careful examination of blood pressures throughout the circulation would indicate that small arteries and arterioles are primarily responsible for resisting blood flow. Investigations at this level of the circulation have either focused on the harvesting of segments of artery or arteriole for in vitro examination or measurements of flow through any artificially isolated part of the body such as an arm or leg in which 70% of the blood is being supplied to skeletal muscle. Such techniques that maximally dilate the circulation have demonstrated an increase in minimal vascular resistance and the evidence is incontrovertible. Folkow has performed elegant studies and advanced the theory that the increase in resistance is caused by structural alterations in the arterial wall, causing luminal narrowing in small arteries. The direct examination of arterial segments either histologically or by mounting them on wires or cannulae and performing morphological measurements have also indicated that the media thickness: lumen diameter ratio of such vessels is increased in hypertension. Indeed, summarising the data from plethysmography, myography and pressure arteriography gives remarkable concordance: the percentage increase in the media thickness: lumen diameter ratio either measured or predicted almost exactly matches the blood pressure increase compared with data from normotensive control subjects. There is also a reduction of 7-8% in the lumen diameter.

Further confirmation that these techniques are complimentary has been provided by a recent study which demonstrated that minimal vascular resistance measured in vivo in the forearm in hypertensive patients closely correlated with the media:lumen ratio of gluteal subcutaneous small arteries. Published work also suggests that these techniques, having been applied to blood vessels which supply the skin and subcutaneous fat, intestine and by extrapolation skeletal muscle, have demonstrated a wide-spread abnormality of vascular structure found in a number of arterial beds. In this context, a recent report has indicated that there are morphological changes in the intramyocardial small arteries of hypertensive patients. In summary, high blood pressure from whatever cause appears to be associated with morphological changes which are found in any vascular bed exposed to the pressure excess.

THE NATURE OF THE STRUCTURAL ALTERATIONS IN SMALL BLOOD VESSELS IN HYPERTENSION

This increased media:lumen ration found in small arteries has been interpreted as being synonymous with a growth response. However, perfusion fixation of the mesenteric arcades from hypertensive and normotensive patients after their death failed to demonstrate an increase in medial cross sectional area. In other words, there was little evidence that the changes had been brought about by hypertrophy of smooth muscle cells within the vascular wall or hyperplastic change of similar tissue elements. Indeed an increased media:lumen ratio can be brought about by re-arranging the existing material around a smaller lumen without the need to invoke a growth response or a change in cross sectional area. This has been termed eutrophic vascular remodelling. Recent histological examination of small arteries harvested from gluteal biopsies appears to confirm that essential hypertension, as we recognise it at present, is associated primarily with eutrophic remodelling with a small contribution from hypertrophy. In other forms of hypertension there is evidence that the proportions of remodelling and growth may vary: in the Ren-II transgenic rat, remodelling appears to be the sole contributor, whereas in aortic coarctation hypertension, there is evidence of hypertrophy in small arteries with luminal narrowing in rat vessels as the pressure rises. In pig coronary vessels exposed to a similar form of experimental hypertension, the predominating mechanism is remodelling.

STRUCTURAL CHANGES: CAUSE OR CONSEQUENCE?

In some respects this is the key question concerning changes in vascular architecture because if they preceded the rise in blood pressure they could serve as vascular amplifiers. What evidence is available at present would suggest that there is a close association between the rise in blood pressure and the structural changes that occur and it is most likely that all the structural alterations occur as a consequence of hypertension. The cellular process that brings about eutrophic remodelling is currently the focus on intense investigation. Using situation where pressure rises and remodelling occurs, evidence is emerging that the myocyte expression of some integrins may change and be responsible for the on-going process of remodelling.

CLINICAL IMPLICATIONS OF VASCULAR CHANGES IN HYPERTENSION

The wide spread small artery structural change induced by hypertension may be of great clinical importance, especially in organs such as the heart where small arteries make a contribution to vascular reserve. Luminal narrowing with eutrophic remodelling would lead to a fixed reduction in the capacity to dilate at times of critical ischaemia, leading to the possibility of dysrhythmias or even patchy necrosis. In consequence, the emphasis is increasingly being placed upon not only controlling blood pressure but ensuring that the agents used are associated with a reversal of this process. If this did not occur, vascular reserve would remain impaired, despite normalisation of blood pressure with the inevitable consequence that the morbidity associated with heart disease would also not necessarily be improved. Data have emerged clearly demonstrating a direct and significant correlation between the degree of small artery vascular change and left ventricular hypertrophy seen in a hypertensive individual. Similarly, the reversal of the increased left ventricular mass index would appear to improve prognosis and the impression gained is that reduction of load and, where possible, reversal of structural change must be associated with improvement in outcome. Small cohort studies have already emerged suggesting that angiotensin converting enzyme (ACE) inhibitors may be superior in this regard but the larger outcome studies will be reported beginning in 1999.

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