H. Thurston

Prior receptor occupancy as a determinant of the pressor activity of infused angiotensin II in the rat.

The pressor responsiveness to angiotensin II and norepinephrine was examined in rats before and during blockade of converting enzyme activity with the nonapeptide SQ 20881. Responses to angiotensin II were impaired by sodium deprivation but enhanced by sodium loading or bilateral nephrectomy. During the period of converting enzyme blockade, a twofold increase in the angiotensin II pressor response was observed in the salt-restricted rats, whereas only a small change occurred in the salt-loaded rats. Infusion of the inhibitor produced a profound fall in the blood pressure of the salt-depleted rats with a relatively minor fall in the sodium-loaded rats. Norepinephrine pressor responses were slightly potentiated in the salt-restricted rats after administration of SQ 20881, but nochange occurred in the salt-loaded or the nephrectomized rats. These observations support the view that the decrease in angiotensin II pressor activity during salt deprivation is the result of a prior occupancy of receptor sites by endogenous hormone. Therefore, a change in the number or the affinity of receptors consequent to changes in sodium balance need not be postulated to explain the phenomenon.

Leucocyte membrane sodium transport in normotensive populations: dissociation of abnormalities of sodium efflux from raised blood-pressure.

Sodium efflux rates were measured in leucocytes from eighteen normotensive subjects who had one or more first-degree relatives with essential hypertension and from twenty-four matched controls with no such family history. The total efflux rate constant was significantly lower in those with a family history of hypertension, owing to reduced ouabain-sensitive sodium pump activity. The presence of a membrane electrolyte handling abnormality characteristic of essential hypertension in normotensive individuals genetically predisposed to hypertension points to an underlying genetic factor. At the same time, the fact that blood-pressure was normal in these subjects indicates that the abnormality does not participate directly in blood-pressure elevation. Rather, the abnormality, like other red-cell changes in electrolyte handling, seems to be a marker for a genetically determined alteration in membrane structure, and thus only indirectly related to hypertension.

Evidence of defective cardiovascular regulation in insulin-dependent diabetic patients without clinical autonomic dysfunction

(1) Autonomic dysfunction is a well recognised complication of diabetes mellitus and early detection may allow therapeutic manoeuvres to reduce the associated mortality and morbidity. We sought to identify early cardiovascular autonomic neuropathy using spectral analysis of heart rate and systolic blood pressure variability. (2) Thirty patients with Type 1 (insulin-dependent) diabetes mellitus (DM) and 30 matched control subjects were studied. In addition to standard tests of autonomic function, heart rate and systolic blood pressure variability were assessed using power spectral analysis. From the frequency domain analysis of systolic blood pressure and R-R interval, the overall gain of baroreflex mechanisms was assessed. (3) Standard tests of autonomic function were normal in both groups. Total spectral power of R-R interval was reduced in the Type 1 DM group for low-frequency (473 +/- 63 vs. 747 +/- 78 ms2, mean +/- S.E.M., P = 0.002) and high-frequency bands (125 +/- 13 vs. 459+/-90 ms2, P < 0.0001). Systolic blood pressure low-frequency power was increased in the diabetic group (9.3 +/- 1.2 vs. 6.6+/-0.7 mmHg2, P < 0.05). The low frequency/high frequency ratio for heart rate variability was significantly higher in the Type 1 DM patients (4.6+/-0.5 vs. 2.9+/-0.5, P = 0.002), implying a relative sympathetic predominance. When absolute powers were expressed in normalised units, these differences persisted. There were significant reductions in baroreceptor-cardiac reflex sensitivity in Type 1 DM patients compared to controls while supine (9.7+/-0.7 vs. 18.5 +/- 1.7 ms/mmHg, P < 0.0001) and standing (2.9+/-0.9 vs. 7.18+/-1.9 ms/mmHg, P < 0.001). (4) Spectral analysis of cardiovascular variability detects autonomic dysfunction more frequently in Type 1 DM patients than conventional tests, and is suggestive of an abnormality of parasympathetic function. The abnormality of baroreceptor-cardiac reflex sensitivity could be explained by this impairment of parasympathetic function and this may predispose to the development of hypertension and increase the risk of sudden cardiac death. Using spectral analysis methods may allow detection of early diabetic cardiac autonomic neuropathy and allow therapeutic intervention to slow the progression.

REVERSIBLE HYPERTENSION AND HYPOTHYROIDISM

Six patients with hypothyroidism and hypertension whose blood pressure fell to normal when treated with thyroxine (172.7.2/112.2.1 to 140.3.2/84.1.6 mmHg, P<0.001) are described. Plasma renin activity (1.76±0.63 ng angiotensin I.ml−1.h−1) was low before treatment. Hypertension with low plasma renin is consistent with sodium retention. Hypertension in the hypothyroid patient only requires further evaluation if it persists after adequate treatment with thyroxine.

TREATMENT OF REFRACTORY HYPERTENSION

126 patients with blood pressure which was unacceptably high despite a conventional stepped-care regimen (diuretic, beta-blocker, and vasodilator) took part in a comparative assessment of different approaches to the treatment of refractory hypertension. One of four regimens was used: oral diazoxide, minoxidil, captopril, or quadruple therapy (diuretic + beta-adrenoceptor blocker + hydralazine + prazosin). Despite the severity of hypertension, blood pressure could be controlled in almost all these patients, and no patient died from cerebrovascular disease while on treatment. 2 patients died of renal failure and 5 patients required long-term haemodialysis. Ischaemic heart disease remained a problem and caused the death of 10 patients. Diazoxide was the most effective treatment but was the most difficult and unpleasant to use. Captopril was the best-tolerated but failed to control blood pressure in 6 of 15 patients. Our experience indicates that there are now sufficient therapeutic alternatives to achieve acceptable blood-pressure control in almost all patients with refractory hypertension, although no treatment is ideal.

Comparison of Angiotensin II Antagonist and Antiserum Infusion with Nephrectomy in the Rat with Two-Kidney Goldblatt Hypertension

Factors responsible for maintaining blood pressure were studied in rats with one renal artery constricted and the contralateral kidney intact. Rats with short-term ( < 3 weeks) and chronic (> 4 months) hypertension were infused with angiotensin II antiserum until the pressor effect of exogenous angiotensin II was blocked. The blood pressure response to an infusion of an angiotensin antagonist (1-Sar-8-Ala-angiotensin II) was then recorded. Blood pressure was also measured following subsequent unilateral nephrectomy (ischemic kidney). Antiserum produced a small, sustained, nonsignificant fall in mean blood pressure, whereas the antagonist produced a major reduction. In rats with short-term hypertension, the antagonist reduced blood pressure to normal or near-normal levels. In rats with chronic hypertension, mean blood pressure fell but still remained above the upper limit of the normal range. Removal of the ischemic kidney produced a fall in blood pressure to a mean level close to that obtained after antagonist infusion. Mean cumulative sodium balance in the rats with short-term hypertension was slightly negative. On the basis of this and previously reported work, it is suggested that angiotensin II is generated at a vascular site which is inaccessible to antibody but readily accessible to antagonist. Moreover, since the effects of angiotensin II antagonist and nephrectomy do not differ significantly, it seems that the ischemic kidney sustains hypertension in this two-kidney model through activity of the renin-angiotensin system, although extrarenal factors assume greater importance when blood pressure remains elevated for longer periods.

Ambulatory Blood Pressure Measurement in Pregnancy: the Current State of the Art

Blood pressure measurement is one of the most frequently used screening tests in pregnancy. However, conventional blood pressure measurement has several shortcomings; it provides a measurement that represents only a fraction of the 24-h blood pressure profile, usually under circumstances that may have a pressor effect, and the technique is fraught with potential errors. In the nonpregnant population the development of devices capable of accurately measuring 24-h blood pressure noninvasively is proving valuable in predicting the cardiovascular complications of hypertension. It is likely that this technique will also prove useful in pregnancy. Validation in pregnancy of such monitoring techniques should precede any widespread application. Reference values using oscillometric monitors are now available for 24-h ambulatory blood pressure measurement in pregnancy. Provisional data suggest that ambulatory blood pressure measurement could overcome the large sampling, measurement, and “white coat hypertension phe...

SALT INTAKE AND DIURETIC TREATMENT OF HYPERTENSION

24 h urinary sodium excretion was used to monitor salt intake in 36 patients with essential hypertension to determine whether limitation of the antihypertensive action of thiazide diuretics could be explained by increased salt appetitie stimulated by salt depletion. Sodium excretion in these patients was similar before treatment to that observed in normotensive controls, and no change was observed during 2 years treatment with bendrofluazide. However, plasma-renin rose progressively over the 2 years even in 5 of 8 patients whose renin was not stimulated initially by diuretics. Thus, there is no evidence that a voluntary increase in salt intake limits the efficacy of diuretic treatment; on the other hand, progressive stimulation of the renin-angiotensin system may be an important limiting factor to the antihypertensive action of diuretics. If so, the antihypertensive effect of dietary salt restriction may be similarly limited.

Labile blood pressure after bilateral carotid body tumour surgery

Introduction We describe a patient with bilateral carotid body tumours that were excised on separate occasions. Following the second procedure the patient developed labile blood pressure that caused significant symptoms. Case Report A 31-year-old woman presented with bilateral neck swellings that had been present for approximately 1 year. Her main symptoms were aching pain on the right side of her neck and a feeling of something in the back of her throat. On examination, there were bilateral swellings in the anterior triangles of the neck. The swelling on the right side was larger and minimally tender. Arteriography confirmed the clin- ical impression of bilateral carotid body tumours and the right-sided tumour was excised without complica- tion. Histology confirmed the diagnosis of benign paraganglioma. Four months later she was readmitted for surgery on the left side. Preoperatively the blood pressure was stable at 110/70mmHg with a pulse of 70/rain. Immediately after excision of the second carotid body tumour the blood pressure was 120/75 mm Hg with a pulse rate of 112/min. During the next 4 days she complained of intermittent frontal headache and was noted to have a persistent sinus tachycardia of between 100 and 140/rain and a blood pressure ranging from 100/60 to 150/100 mm Hg. These symp- Please address all correspondence to: N.J.M. London, Department of Surger~ Clinical Sciences Building, Leicester Royal Infirmar~ Leicester, LE2 7LX, U.K. toms improved with simple analgesia and she was discharged home with a provisional diagnosis of bilateral damage to the carotid sinus sympathetic afferent nerves. She was also noted to have a left hypoglossal nerve neuropraxis which resolved by 2 weeks. When the patient returned to clinic 1 month later she had experienced a number of problems. She complained of palpitations, flushing and recurrent severe frontal headaches. On three occasions the headaches had been followed by loss of consciousness for a few minutes and resulted in her being rushed to her local Accident and Emergency department where she was found to be markedly hypertensive. On examination in clinic she had an erythematous rash over her upper trunk, a pulse rate of 84/rain and a blood pressure of 160/100mmHg. At this stage ambulatory blood pressure monitoring and 24 h uri- nary collections for catecholamines to exclude the possibility of a phaeochromocytoma were arranged. On arrival in clinic 3 weeks later she complained of a severe frontal headache and promptly fainted. Her blood pressure at the time was recorded as 210/128mmHg. She was therefore admitted for fur- ther investigation. The 24h urinary collections showed no excess catecholamines. The ambulatory blood pressure monitoring demonstrated considerable variations in both blood pressure and pulse rate during a 24h period (Fig. 1). Discussion Arterial blood pressure is controlled by several inter- related systems. Baroreceptors are nerve endings that lie in the walls of arteries and are stimulated when 1078-5884/95/030346 + 03

Renin in the Arterial Wall

08.00/0