J. J. Brown

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.

Combined treatment of severe intractable hypertension with captopril and diuretic.

The converting-enzyme inhibitor, captopril, in a dose of 450 mg daily, was given together with a diuretic to eleven patients with severe hypertension unresponsive to previous therapy. Sustained control of blood pressure was achieved. Plasma angiotensin II and aldosterone fell significantly, whereas plasma active and total renin, and blood-angiotensin-I concentrations increased. Adverse effects included temporary taste disturbance, tachycardia, nephrotic syndrome, and possible drug-induced Guillain-Barré neuropathy. The combination of captopril and diuretic is thus very effective in controlling refractory hypertension. However, because of the frequency and severity of side-effects it should probably be used only in patients whose blood pressure has previously been uncontrolled by other means.

Blood pressure in acute and chronic vasopressin excess: studies of malignant hypertension and the syndrome of inappropriate antidiuretic hormone secretion.

We studied 29 patients with malignant hypertension and 28 patients with the syndrome of inappropriate antidiuretic hormone secretion to assess the relation of plasma vasopressin to blood pressure in states of acute and chronic vasopressin excess. In the patients with malignant hypertension, vasopressin levels were elevated (13 +/- 2 pg per milliliter. [+/- S.E.M.]) but did not correlate with arterial pressure; however, in normal volunteers, blood pressure did not rise when vasopressin was increased beyond these levels through infusion of the peptide. In the patients with inappropriate antidiuretic hormone secretion, blood pressure was not elevated, but vasopressin was raised (39 +/- 7 pg per milliliter) and did not correlate with systolic or diastolic pressure. These data do not support the concept that an acute or chronic excess of vasopressin makes an important contribution to the regulation of blood pressure.

CHANGES OF VASOPRESSIN IN HYPERTENSION: CAUSE OR EFFECT?

Plasma concentrations of arginine-vasopressin (antidiuretic hormone) have been measured in 40 patients with benign essential hypertension and 12 patients with malignant-phase hypertension. Values tended to be low in the benign phase and high in the malignant phase. 5 normal subjects were infused with synthetic arginine-vasopressin, producing plasma concentrations up to five times the highest value recorded in malignant-phase hypertension, without any effect on blood-pressure. There is no evidence that vasopressin has a direct role in the pathogenesis of benign essential hypertension or its transition to the malignant phase. On the contrary, abnormal vasopressin concentrations may be caused by hypertension.

Hypertension with aldosterone excess and low plasma-renin: preoperative distinction between patients with and without adrenocortical tumour.

Abstract A retrospective analysis of thirty-four patients with hypertension, hyperaldosteronism, and low plasma-renin is described. A single adrenocortical adenoma was found in twenty. No tumour was seen in eleven, and the adrenal glands of nine of these showed hyperplasia of the zona glomerulosa. A definite pathological diagnosis was not possible in three patients. Mean plasma concentrations of aldosterone, sodium, and total carbon dioxide were higher, while mean plasma concentrations of renin and potassium were lower in the tumour group, when compared with non-tumour patients. These differences were seen both in patients taking a controlled constant intake of sodium and potassium and in patients taking a normal unrestricted diet. Considerable overlap in each of the variables was found among individual patients, and straightforward analysis of the preoperative biochemical data did not permit a confident prediction of the adrenal lesion. However, a multidimensional computer-assisted analysis enabled complete separation of tumour and non-tumour groups and it is suggested that this technique may be of value in making the preoperative distinction in future cases.

Hyponatraemic hypertensive syndrome with renal-artery occlusion corrected by captopril.

Malignant hypertension with severe hyponatraemia, hypokalaemia, depletion of sodium and potassium, and elevated blood levels of renin, angiotensin I, angiotensin II, aldosterone, and arginine vasopressin developed in a woman with renal-artery occlusion. Plasma angiotensin II was disproportionately high in relation to exchangeable sodium. Captopril, by inhibiting conversion of angiotensin I to angiotensin II, further elevated the blood levels of renin and angiotensin I but corrected all other abnormalities. Unilateral nephrectomy was subsequently curative.

The relation of arterial pressure and plasma angiotensin II concentration. A change produced by prolonged infusion of angiotensin II in the conscious dog.

Five unrestrained male beagle dogs were given a continuous intravenous infusion for 28 days. First, 0.9% NaCl solution was infused for 7 days, then angiotensin II at 3 ng/kg per min for 14 days, and finally 0.9% NaCl for 7 days. We found that the blood pressure rose gradually in each dog, reaching a peak toward the end of the 14-day infusion of angiotensin IL When angiotensin infusion was stopped, blood pressure fell gradually during 24 hours; the lowest pressure was not reached until 5 days later. To assess the relation between plasma angiotensin II concentration and arterial pressure, dose-response studies were done during the first saline infusion, after 7 and 14 days of angiotensin II infusion, and at the end of the second saline infusion. In these experiments, additional angiotensin II was infused intravenously at 3, 6, and 12 ng/kg per min, each rate for 1 hour. The increase of arterial pressure was then related to concurrent plasma angiotensin II concentration. In all dogs, prolonged infusion of angiotensin shifted the position of this curve upward. Thus, prolonged infusion of angiotensin raised the level of pressure maintained by a given plasma concentration of angiotensin EL Seven days after the angiotensin infusion, the curve had returned to the original position. Plasma aldosterone concentration also increased during all dose-response studies. The slope of the regression curve relating plasma concentrations of angiotensin II and aldosterone was steeper after, but not during, prolonged infusion of angiotensin EL Plasma potassium concentration did not change at any stage. Ore Res 44: 462-458, 1979

PLASMA ELECTROLYTES, RENIN, AND ALDOSTERONE IN THE DIAGNOSIS OF PRIMARY HYPERALDOSTERONISM: With a Note on Plasma-corticosterone Concentration

Abstract Plasma electrolytes, renin, and aldosterone concentrations were measured in 50 patients with primary hyperaldosteronism. Although plasma-potassium concentration varied over a considerable range in most cases, the levels were consistently lower than 3·7 meq. per litre in 27 patients, and intermittently so in all but 1 of the remainder. It is particularly important to avoid forearm exercise immediately before venepuncture if falsely high potassium values are to be avoided. Plasma-renin concentration was subnormal at least once in 42 patients, and consistently so in 24 of these. The remaining results were normal, most of them falling near the lower limit observed in normal subjects. In several cases sodium restriction caused distinct increases in plasma-renin concentration, and in 1 patient the final level was within the range found in sodium-deprived normal subjects. Plasma-aldosterone concentration was abnormally high on at least one occasion in 38 of the 39 patients in whom it was measured.

Quadric analysis in the preoperative distinction between patients with and without adrenocortical tumors in hypertension with aldosterone excess and low plasma renin

Abstract Retrospective assessment by means of computer-assisted quadric analysis of a series of 31 patients with aldosterone excess and low plasma renin permitted complete separation into two groups—those with, and those without adrenocortical adenoma. Application of these principles to 8 more patients was successful in all cases in correctly diagnosing the type of pathological lesion before operation. Study of four similar published series has shown that each of these could also be accurately differentiated into the two diagnostic categories by quadric analysis. However, probably because of interlaboratory variation, internal analysis using circumscribing quadrics established for each series individually was much more reliable than external analysis with reference to the quadrics of the original series. Quadric analysis, by enabling a confident prediction to be made before operation as to the presence or absence of an adrenocortical adenoma, has major value in the practical management of these patients. In particular, in the cases without adenoma, long-term or definitive spironolactone therapy may now be offered as a valid alternative to extensive bilateral adrenal resection. It is further suggested that the technique of quadric analysis is likely to have wide application in other diagnostic areas.

Blood pressure and plasma angiotensin II concentration after renal artery constriction and angiotensin infusion in the dog. (5-Isoleucine)angiotensin II and its breakdown fragments in dog blood.

We measured arterial plasma angiotensin II concentration, renal blood flow, and arterial blood pressure in six conscious dogs during intravenous infusion of angiotensin II (5, 10, and 20 ng/kg per min). The same measurements were made on a different occasion in the same six animals, while they were conscious, before and during constriction of a main renal artery. Arterial blood pressure and plasma angiotensin II rose and renal blood flow decreased in both experiments. The similarity of regressions for plasma angiotensin II concentration and arterial blood pressure in the two experiments strongly suggests that the rise of circulating angiotensin II after renal artery constriction is sufficient to account for the hypertension by its direct pressor action. As discussed, a different mechanism seems likely to be involved in the later stages of renal hypertension. Angiotensin II is more likely to be in the 5-isoleucine form than in the 5-valine form in the dog. In contrast to the rat, plasma concentrations of the heptapeptide (angiotensin III), hexa-peptide, and pentapeptide fragments of angiotensin II are low in the dog.