Assessment of the contributions of autoregulatory mechanisms to the antihypertensive actions of beta-adrenergic therapy.

T HE study by Colfer et al.' in this issue of Hypertension again raises the issue of whether whole-body autoregulation plays a role in determining overall changes in total peripheral resistance (TPR) during the development or reversal of hypertension. This hypothesis remains controversial because the local tissue mechanisms responsible for either the functional alterations in smooth muscle vascular tone or the long-term restructuring of vascular beds seen in hypertension are poorly understood. This does not mean, however, that the hypothesis is not based upon a reasonable extrapolation of solid biological data. Rapid local control, or "autoregulation" of tissue blood flow, has been characterized in nearly every organ system of the body. That is, either overor underperfusion of an isolated tissue bed, brought about by raising or lowering the regional blood perfusion pressure, results in local adjustments of vascular resistance which return blood flow toward normal levels. Over the past 20 years, physiologists interested in the microcirculation have been preoccupied by these events. We have used the term longterm autoregulation, as reviewed elsewhere, to describe the observed vascular responses that occur over days and months.The question is not whether local regulation of vascular resistance occurs. Rather, are such mechanisms of sufficient strength to effect long-term changes of TPR in the intact oganism? And, how do these mechanisms operate? The challenge has been, and remains, to develop techniques that can selectively determine the relative importance of various local factors that influence both acute and long-term control of regional blood flow. It is easy to play the role of devil's advocate in this issue, since so many fundamental mechanisms regulating tissue blood flow remain a mystery. So far, the carefully controlled studies of regional and/or whole-body autoregulation have all examined responses within time frames that are very brief in nature (1 minute to 3 hours). Whether these responses persist over prolonged periods, such as days and months, remains to be determined. It is also not known whether the acute autoregulatory responses are replaced, overridden, or altered in sensitivity by long-term structural changes. Physiologists interested in the microcirculation have demonstrated that considerable regional vascular heterogeneity exists. This raises the question of which vascular beds should best be studied. Recent data by Liard indicate that, in response to chronic blood volume expansion, nearly all body organs and tissues constrict very rapidly to normalize blood flow and then sustain these increases in vascular resistance for prolonged periods. An exception to this was skeletal muscle, which remained overperfused for several days before it gradually increased its resistance to flow. Liard's