title: The second Sir George Pickering memorial lecture. What regulates whole body autoregulation? Clinical observations.
abstract: The autoregulation theory of essential hypertension states that the characteristic haemodynamic derangement of this disease, i.e. increased vascular resistance, is a homeostatic response to abnormal sodium retention by the kidneys. The postulated relationship between arterial pressure and urinary sodium excretion is disturbed in such a way that a higher than normal pressure is required for sodium excretion to keep up with intake. This will initially expand plasma volume and raise cardiac output. However, hyperperfusion of the tissues will ultimately induce vasoconstriction, presumably by greater than normal wash-out of vasodilator metabolic products. Thus, cardiac output will be restored. Some elements of this theory are not supported by current evidence, but the key element, i.e. the assumption that increased vascular resistance is somehow dependent on abnormal renal sodium handling, is consistent with the following clinical observations: Arterial pressure and urinary sodium excretion are directly correlated over a wide range of pressures in patients with autonomic failure, both acutely during titling and chronically with changes in posture during a 24-h period. The failure to demonstrate pressure-natriuresis in normal subjects may therefore be related to the amplifying effect of the sympathetic nervous system on this mechanism, so that small changes in pressure are capable of inducing large changes in sodium excretion. The pressure-natriuresis curve in patients with autonomic failure is shifted to higher pressures by administration of aldosterone, which is consistent with an important role of renal sodium retention in mineralocorticoid hypertension. Measurements of total extracellular fluid volume, plasma volume/interstitial fluid volume ratio, transcapillary escape rate of serum albumin, cardiac output and arterial pressure at timed intervals during the development of hypertension, in patients exposed to mineralocorticoid excess, or during the reversal of hypertension in nephrectomized patients treated with ultrafiltration haemodialysis, revealed an association of increased total peripheral resistance with a reduced plasma volume/interstitial fluid volume ratio and an increased transcapillary escape rate of serum albumin. This association has also been observed in cross-sectional studies of patients with essential hypertension and suggests that part of the increase in resistance is located at a post-capillary level. It may be related to compression of collapsible venules and veins due to abnormally increased interstitial fluid pressure, not only in sodium-dependent secondary forms of hypertension but also in essential hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000494:pharmacology; D001342:Autonomic Nervous System Diseases / Q000150:complications / Q000503:physiopathology; D001794:Blood Pressure; D001826:Body Fluids; D002302:Cardiac Output; D005438:Fludrocortisone / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D009392:Nephrectomy; D006435:Renal Dialysis; D014655:Vascular Resistance
chemical_list: D000450:Aldosterone; D005438:Fludrocortisone