F. Arzilli

Endothelium-dependent forearm vasodilation is reduced in normotensive subjects with familial history of hypertension

Summary: Endothelium‐dependent vasodilation is reduced in essential hypertensive subjects. To evaluate whether this abnormality is a primary defect or is a consequence of blood pressure increment, in offspring of essential hypertensive and normotensive subjects (n = 13 subjects for each group) matched for age, sex, body weight, and blood pressure, we studied the response of forearm vasculature to acetylcholine (ACh) (an endothelium‐dependent vasodilator), sodium nitroprusside (a direct vasodilator of vascular smooth muscle), and forearm ischemia (13 min plus 1 min of exercise) to induce maximal vasodilation. Drugs were infused into the brachial artery at cumulative doses (ACh: 0.15, 0.45, 1.5, 4.5, and 15 μg/100 ml of forearm tissue/min; sodium nitroprusside: 1, 3, and 10 μg/100 ml of forearm tissue/min) while forearm blood flow was measured by strain‐gauge venous plethysmography. The intra‐arterial blood pressure and heart rate were continuously monitored. Despite a comparable forearm vascular response to sodium nitroprusside and to forearm ischemia, the effect of ACh was significantly (p < 0.001) reduced in offspring of hypertensive subjects compared to the offspring of normotensive subjects. These data indicate that ACh‐mediated forearm vasodilation is reduced in normotensive subjects with a familial history of essential hypertension, a finding that suggests that endothelium dysfunction can precede the appearance of hypertension and that this abnormality might play a role in the pathogenesis of essential hypertension.

Interaction between oxprenolol and indomethacin on blood pressure in essential hypertensive patients.

SummaryA double-blind, cross-over study in 16 patients with essential hypertension was carried out, to evaluate any possible interference by indomethacin, a known prostaglandin-synthetase inhibitor, with the antihypertensive effect of oxprenolol, a non-selective beta-adrenoceptor blocking agent. Both indomethacin and oxprenolol, as well as the two drugs combined, inhibited plasma renin activity; no change was found in urinary sodium excretion or body weight. Oxprenolol alone caused a highly significant decrease in the systolic (−10.4 mmHg,p<0.001), diastolic (−7.4 mmHg,p<0.001) and mean (−7.7 mmHg,p<0.01) blood pressures, whereas indomethacin did not influence blood pressure. When the two drugs were given in combination, blood pressure decreased (systolic: −5.9 mmHg; diastolic: −4.0 mmHg; mean: −4.6 mmHg), but the changes induced in blood pressure were reduced by about 50% when compared with those in the oxprenolol alone period. The data show that indomethacin seems to interfere with the antihypertensive effect of oxprenolol, by an action which may be due to the inhibition of prostaglandin synthesis.

Microalbuminuria and renal haemodynamics in essential hypertension

The present study was designed to evaluate the renal haemodynamic pattern of never‐treated microalbuminuric and normoalbuminuric patients with essential hypertension. A total of 19 never‐treated essential hypertensive patients with microalbuminuria were selected and, as control subjects, 24 never‐treated essential hypertensive patients without microalbuminuria (determined on three 24‐h urine collections) were recruited. In the two groups, we compared blood pressure values, standing plasma noradrenaline, plasma renin activity, plasma aldosterone, urinary aldosterone, lipid profile, serum glucose and uric acid, glomerular filtration rate and renal plasma flow. In comparison with normoalbuminuric patients, microalbuminuric patients showed significantly higher systolic blood pressure values (P < 0.05), higher renal vascular resistances (P < 0.05) and lower plasma renin activity values (P < 0.01). Urinary albumin excretion showed a significant positive correlation with systolic (r = 0.46, P < 0.005) and mean blood pressure (r = 0.38, P < 0.05), serum uric acid (r = 0.43, P < 0.005) and triglyceride values (r = 0.36, P < 0.005), and a significant negative correlation with plasma renin activity (r =  − 0.34, P < 0.05). The present data are consistent with the occurrence of renal vasoconstriction in microalbuminuric never‐treated essential hypertensive patients.

Influence of indomethacin on the natriuretic and renin-stimulating effect of bumetanide in essential hypertension.

The effect of bumetanide on absolute and fractional sodium excretion, creatinine clearance, and plasma renin activity (PRA) was studied in eight patients with essential hypertension before and after indomethacin. After bumetanide, urinary sodium excretion increased only in the first 4 hr, creatinine clearance only in the first 2 hr, and PRA rose progressively. After indomethacin, bumetanide caused a smaller increase in urinary sodium excretion, decreased creatinine clearance, and caused a small early and late PRA rise. Prostaglandin inhibition and indomethacin did not, per se, affect the tubular natriuretic mechanism but they abolished both early vascular and sustained PRA‐stimulating effects of bumetanide.

Influence of Age and Sodium Intake on Plasma Renin Activity of Normal Subjects

Supine and upright plasma renin activity (PRA) were measured i 104 normal subjects (age range 13-74 years, 71 males and 33 females) on a constant diet of normal potassium (60-80 mEq/day) and of varying but constant, sodium content (range 10-260 mEq/day). Both supine and upright PRA values were inversely related to the 24-hour urinary sodium excretion, while only upright PRA values showed a significant inverse correlation with age. Through a multiple regression analysis it was shown that age increased the significance of the PRA/sodium relationship by about 10%. Besides posture, two other factors seem to influence the PRA-age relationship: the age range and the sodium intake. In fact, the PRA-age relationship was not detectable either when subjects below 20 and above 50 were excluded, or when sodium intake was increased above 140 mEq/day. These data can explain the contrasting reports on the age influence on renin secretion. The relationship between PRA and urinary sodium confirms the dependance of PRA on the state of sodium balance. Age significantly influences the PRA/sodium relationship of normal subjects on normal or low sodium intake and in the upright position. Therefore, the decline of PRA with age may be explained by the decrease either of renin storage or of sympathetic nervous system activity on renin release.

Effects of salbutamol and metoprolol on plasma renin activity and plasma potassium of normal subjects and of hypertensive patients

The effect of β2-agonist salbutamol on plasma renin activity (PRA) and plasma potassium was investigated in seven normal subjects, in twenty-three patients with essential hypertension and in one patient with primary aldosteronism. The action of β1-antagonist metoprolol on PRA and plasma potassium changes induced by salbutamol was also studied in one normal subject and in seven patients with essential hypertension. Salbutamol significantly increased PRA in normal subjects and in patients with essential hypertension with normal (8 cases) or high (5 cases) PRA, while it did not modify PRA in patients with essential hypertension with low PRA (10 cases), and in the patient with primary aldosteronism. Plasma potassium was significantly decreased after salbutamol both in normal and hypertensive patients: no correlation was found between PRA and plasma potassium changes. Metoprolol inhibited both PRA increments and plasma potassium decrements induced by salbutamol. These data suggest the following conclusions. β-Adrenergic receptors mediating renin release in man cannot be clearly differentiated into β-subtypes. The PRA unresponsiveness observed in patients with essential hypertension with low PRA and in the patient with primary aldosteronism indicates a decreased renal response to adrenergic stimuli, probably due to a decreased renin storage. The hypokalemic action of salbutamol cannot be explained by changes of the renin angiotensin system. Moreover the β-receptors mediating the decrease of plasma potassium cannot be clearly differentiated into β-subtypes.

Renovascular hypertension and insulin sensitivity

We tested the hypothesis that the status of the renin–angiotensin–aldosterone system affects insulin sensitivity. Insulin sensitivity (by the euglycaemic insulin clamp technique) was measured in eight patients with angiographically proven renovascular hypertension and in eight normotensive subjects matched for age, gender, body mass index and glucose tolerance. In the patients, insulin sensitivity was measured both at baseline and following 7 days of ACE inhibition. Following glucose ingestion, patients and controls showed similar insulin and glucose responses. Insulin infusion (7 pmol min−1 kg−1) promoted similar glucose utilization in the hypertensives and normotensives: 24.8±2.3 vs. 26.0±3.0μmol min−1 kg−1 respectively. One week of ACE inhibition caused a 20±4 mmHg decrease in mean blood pressure and a 20±6% decrease in peripheral vascular resistance. Plasma angiotensin II concentrations dropped from 24.6±6.3 to 13.5±5.0 pg mL−1 (P<0.05) and plasma aldosterone from 17<4 to 92 ng dL−1 (P<0.05), and plasma renin activity doubled (from 1.6±0.3 to 3.4±1.7 ng mL−1 h−1P<0.02). Nevertheless, insulin sensitivity was unchanged (before, 24.8±2.3; after, 25.8±2.2μmol min−1 kg−1P=Ns). During insulin infusion, forearm blood flow did not change from baseline in either set of studies. Also, the antinatriuretic (before, −26±18; after, −22±14%) and antikaliuretic (before: −36±13%, after: −39±11%) action of the hormone was unaffected by the therapy. In conclusion, human renovascular hypertension is not associated with insulin resistance. Furthermore, a selective, drastic reduction of the renin–angiotensin‐aldosterone system activity and vascular tone does not alter insulin action on glucose and electrolyte metabolism.

Renal Vein Renin in Renovascular Hypertension: The Experience of Two Italian Centers

A retrospective analysis of renal vein renin results has been done in 96 patients with renal artery stenosis and hypertension studied in two Italian centers (Sassari and Pisa) with respect to the outcome of either surgery or percutaneous transluminal angioplasty (PTA). In all patients the renal vein renin ratio and the V-A/A ratios for the affected and unaffected kidney were calculated. Each patient underwent surgery (75) of PTA (21): 71 subjects were cured, 17 improved whereas the arterial pressure did not vary after revascularisation procedure in 8 patients. In the Pisa series all 54 patients showed a lateralisation with contralateral renin suppression and 95% of them benefitted from surgery. In the Sassari series 42 patients were submitted to PTA or surgery, not only on the basis of a positive renal vein renin study but taking into account a complete clinical evaluation: 8 of them were cured or improved in spite of negative renal vein renin criteria. In the two series, the better predictive index appeared to be the suppression of the renin secretion from the contralateral kidney while the high/low renin ratio showed a consistent amount of false-positive and false-negative results. Our retrospective study demonstrates that the renal vein test in hypertensive patients with renal artery stenosis is highly predictive of the curability of the disease, particularly when contralateral suppression of renin secretion is present. On the other hand, since patients with negative renin indexes can also take benefit from surgery of PTA, the renin parameters cannot be adopted as the sole criterion in making the decision to operate.

Lack of effect of percutaneous transluminal renal angioplasty on nocturnal hypotension in renovascular hypertensive patients

Objective To investigate whether nocturnal blood pressure fall is blunted in renovascular hypertension and can therefore be used as a diagnostic criterion for this condition. Methods In 14 renovascular hypertensive patients (age 43.8±2.1 years, mean±SEM, clinic blood pressure 173.6±3.7mmHg systolic and 109.0±2.0mmHg diastolic) and in 14 age- and blood pressure-matched essential hypertensive controls 24 h ambulatory blood pressure was measured after washout from drug treatment, during angiotensin converting enzyme inhibitor treatment and, in renovascular hypertension, also after percutaneous transluminal renal angioplasty. Results The 24 h average systolic and diastolic blood pressures were 146.4±5.7 and 97.5±3.6mmHg in renovascular and 144.3±1.2 and 98.0±2.2mmHg in essential hypertensive patients. The angiotensin converting enzyme inhibitor treatment reduced 24 h average systolic and diastolic blood pressures by 8.5% and 9.7% in the renovascular and by 8.3% and 10.8% in the essential hypertensive group. Greater systolic and diastolic blood pressure reductions (-18.2% and −18.1%) were observed in renovascular hypertensive patients after percutaneous transluminal renal angioplasty. Blood pressure fell by about 10% during the night and the fall was similar in renovascular and in essential hypertensive patients. In the former group, nocturnal hypotension was similar after washout, during angiotensin converting enzyme inhibitor treatment and after percutaneous transluminal renal angioplasty. Similar results were obtained for nocturnal bradycardla. Conclusions Nocturnal blood pressure fall is equally manifest in renovascular and essential hypertension. The removal of the renal artery stenosis and blood pressure normalization do not enhance this phenomenon. Nocturnal hypotension seems therefore to be unaffected by renovascular hypertension.

The effect of beta-adrenergic blockade on patterns of urinary sodium excretion, blood pressure and plasma renin activity in patients with essential and renovascular hypertension.

Abstract. The effects of β‐adrenergic blockade, using oxprenolol, were studied on plasma renin activity, urinary sodium excretion and blood pressure in ten normal subjects and in 120 patients with essential and renovascular hypertension.