M.A. Schalekamp

ABNORMAL RELATION BETWEEN EXCHANGEABLE SODIUM AND THE RENIN-ANGIOTENSIN SYSTEM IN MALIGNANT HYPERTENSION AND IN HYPERTENSION WITH CHRONIC RENAL FAILURE

Abstract Exchangeable sodium and plasma levels of renin and angiotensin II were measured in patients with normal blood-pressure and in patients with hypertension, either in the malignant phase or associated with chronic renal failure. In normotensive subjects exchangeable sodium correlated inversely with plasma-renin concentration and with plasma-angiotensin-II. Abnormally high levels of renin and angiotensin II, relative to exchangeable sodium, were found in the hypertensive patients. This accords with the suggestion that renin release, inappropriately high in relation to sodium balance, may raise blood-pressure in certain types of hypertension.

MECHANISM OF RENAL HYPERTENSION

Renal hypertension of the two-kidney type is divided into three stages. In the first, hypertension results from the vasoconstrictor effect of angiotensin II. This persists to some extent in the second phase but there is in addition a slow-developing pressor effect, also resulting from angiotensin II and probably attributable to sodium. In the first two phases removal of the abnormal kidney corrects the hypertension. This fails in the third phase because changes in the opposite kidney maintain hypertension. Renin and angiotensin are probably not involved at this stage.

IS LOW-RENIN HYPERTENSION A STAGE IN THE DEVELOPMENT OF ESSENTIAL HYPERTENSION OR A DIAGNOSTIC ENTITY ?

A study of the frequency distribution of plasma-renin concentration in 81 patients with essential hypertension produced no evidence of a distinct sub-population with low renin levels. An arbitrary dividing line was used, therefore, to define low-renin hypertension (36% of patinets). Patients in this group were older than those with normal renin levels, and there was a significant negative correlation between renin and age among all patients. Low-renin hypertension was not characterized by increased exchangeable sodium, but exchaneable postassium was significantly lower than in patients with normal plasma-renin. This difference became insignificant when five patients in the low-renin group with persistent hypokalaemia were excluded. It is concluded that low-renin hypertension does not represent a separate diagnostic entity but that plasma-renin falls with age in essential hypertension.

BODY-FLUID VOLUME IN LOW-RENIN HYPERTENSION

Abstract Plasma and extracellular-fluid volumes were normal in thirty-eight patients with normal-renin hypertension and in seventeen patients with low-renin hypertension, there being no difference between the two groups. This strongly suggests that reduction of renin in low-renin hypertension is not brought about by sodium retention with volume expansion.

Sodium and the renin-angiotensin system in essential hypertension and mineralocorticoid excess.

Abstract Exchangeable sodium (NaE) was increased in untreated primary hyperaldosteronism but normal in treated primary hyperaldosteronism and in untreated essential hypertension, low-renin hypertension, and hypertension with excess 11-deoxycorticosterone ( D OC). The relation between NaE and plasma-renin was normal in essential hypertension and primary hyperaldosteronism but subnormal in low-renin hypertension and DOC excess. Depression of renin in low-renin hypertension cannot therefore be attributed to abnormal sodium retention.

RENAL ABNORMALITY OF ESSENTIAL HYPERTENSION

Abstract Although homœostatic mechanisms relate sodium balance, renin, and arterial pressure, the reduction of renin sometimes seen in essential hypertension cannot be attributed to abnormal sodium retention. It is proposed instead that renin decreases and sodium status remains normal because the pressure-natriuretic mechanism within the kidney is reset by increased filtration fraction. Neurogenic factors may raise blood-pressure and cause resetting by some other means at an early (labile) stage of essential hypertension, but, once filtration fraction is raised and remains elevated on withdrawal of the neurogenic component, essential hypertension will have a renal cause. A similar mechanism may account for the failure of secondary hypertension to fall when its cause is removed.

CONSECUTIVE HÆMODYNAMIC PATTERNS IN ESSENTIAL HYPERTENSION

Abstract Fifteen patients with essential hypertension were investigated twice (and in three cases three times), the average interval between the first and the final examination being 31 months (range 11-54 months). Arterial pressure and one or several of the following variables were measured or calculated: cardiac output, renal plasma-flow, glomerular filtration-rate, plasma volume, variability of blood-pressure, renal blood-flow, total peripheral resistance, renal vascular resistance, filtration fraction, and blood volume. In twelve patients no complications were observed. The other three had a myocardial infarction during the observation period. Patients were taken off treatment before the investigations were done and sodium intake was controlled. Even within this rather short follow-up period some radical changes in haemodynamic patterns were demonstrated. In eight of the twelve uncomplicated cases either total peripheral resistance or renal vascular resistance or both increased. The three patients who sustained a myocardial infarc tion all showed a shift towards increased vascular resistance.

Pathogenesis of essential hypertension.

It is proposed that essential hypertension is an exaggeration of the tendency for blood-pressure to rise with age, that it results from a repeated sequence in which a small rise in pressure, possibly resulting from an autonomic nervous overactivity, produces changes in the kidney which maintain the rise of pressure and become the basis for a further rise.

INTERRELATIONS BETWEEN ARTERIAL PRESSURE, FLUID-VOLUMES, AND PLASMA-RENIN CONCENTRATION IN THE COURSE OF ACUTE GLOMERULONEPHRITIS

Abstract Two patients with acute glomerulonephritis and hypertension exhibited a normal cardiac output despite excessive fluid retention and hypervolaemia. Plasma-renin concentration at first was subnormal in one patient and normal in the other. In both, plasma-renin rose steeply to abnormal levels after the onset of unloading. One patient was given an artificial load afterwards; plasma-renin then fell to a much lower level than was found in the first stage. It is suggested that an inappropriate renin secretion both increased peripheral resistance and inhibited prompt reversion of blood-pressure towards a normal level.

Inter-relationships between plasma angiotensin II, arterial pressure, aldosterone and exchangeable sodium in normotensive and hypertensive man

Abstract 1. 1. Evidence bearing on the importance of the renin/angiotensin system in the regulation of aldosterone secretion in man is reviewed. 2. 2. Elevation of plasma angiotensin II concentration in simple dietary sodium deprivation has been confirmed. 3. 3. In primary renin deficiency, both angiotensin II and aldosterone are deficient. In these circumstances plasma aldosterone can remain unresponsive to very large rises in plasma potassium, but increase promptly on infusion of angiotensin II. 4. 4. Sodium depletion in normal man increases the adrenocortical sensitivity to angiotensin II, while diminishing the presser effect. 5. 5. The Na E /renin and Na E /angiotensin II interrelations are normal in primary hyper-aldosteronism both before and after treatment, and also in untreated essential hypertension with normal renin levels. 6. 6. These relationships are depressed in low-renin essential hypertension. 7. 7. In renal and malignant hypertension the relationships are enhanced. 8. 8. In renal and malignant hypertension the angiotensin II-pressor relationship is enhanced, and the angiotensin II-aldosterone relationship steepened as compared with normal subjects acutely infused with angiotensin. 9. 9. A hypothetical mechanism for the suppression of renin in essential hypertension is outlined.