Biomedical subjects
J W Hollifield
Publications and source records attributed to J W Hollifield.
Biochemical consequences of diuretic therapy in hypertension.
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Sustained hypertension after section of the glossopharyngeal nerve.
A case of sustained hypertension produced by unilateral section of the glossopharyngeal nerve is reported. Special tests revealed baroreceptor dysfunction. The hypertension was responsive to propranolol therapy. Review of the literature revealed no other documented cases of sustained hypertension although transient hypertension is common.
The C19-mineralocorticoids in hypertension.
The excretion rates of the C19-mineralcorticoids, 16beta-hydroxy-DHEA and 16-oxo-androstenediol, were measured in subjects with low-renin essential hypertension and toxemia of pregnancy. C19-mineralocorticoid excretion in low-renin essential hypertension ranged from 70-790 microgram per day. No significant difference in 16beta-hydroxy-DHEA and 16-oxo-androstenediol excretion was found between these subjects and normal controls. Subjects with toxemia of pregnancy excreted between 350 and 2500 microgram per day of these steroids. There was no significant difference between toxemic and normal pregnancy. Thus, 16beta-hydroxy - DHEA and 16-oxo-androstenediol probably do not play an important role in either low-renin essential hypertension or toxemia of pregnancy.
Saralasin infusion in the recognition of renovascular hypertension.
Saralasin, an angiotensin II antagonist, was infused into 49 patients with renal artery stenosis, 10 patients with essential hypertension and normal renal arteriograms, and five patients with "low-renin essential hypertension." Renal venous renin and differential renal function studies were used to assess the functional significance of arterial stenoses. "Response" to saralasin, evidenced by a fall in blood pressure during infusion, occurred in no patients with "low renin" hypertension and in only 20% of patients with normal renal arteriograms. In contrast, saralasin "response" occurred in more than 80% of patients with renal artery stenosis and lateralizing functional studies and 100% of cases of "proven" renovascular hypertension (cure or improvement of hypertension after operative treatment). We suggest that saralasin infusion might be a valuable screening test for the recognition of renovascular hypertension.
Bilateral renal artery stenosis and renovascular hypertension.
Experience with the diagnostic evaluation and operative management of 38 hypertensive patients having bilateral renal revascularization is presented. Twenty-four patients had atherosclerotic occlusions and 14 had fibromuscular dysplasia. Renal vein renin assays (RVRA) and/or split renal function studies (SRFS) were performed in 37 of the 38 patients before operation. Although RVRA was negative in 29 percent and SRFS negative in 31 percent, 24 of 26 patients (92 percent) having both tests done had at least one positive study. Twenty-one patients had simultaneous bilateral repairs and 12 had staged bilateral reconstructions. The incidence of technical failures in these two groups was 21 and 9 percent, respectively. Excluding three uncorrected technical failures and two patients with recurrent branch renal artery lesions, 90 percent of patients with atherosclerosis and all patients with fibromuscular dysplasia had a favorable blood pressure response to operation. This study supports the use of both RVRA and SRFS in the diagnostic evaluation of hypertensive patients with renal artery stenosis. If these functional tests lateralize to one side, repair of that side only is recommended. If the functional studies do not lateralize, operation is suggested only when hypertension is severe and is not controlled readily with medications. In this circumstance reconstruction of the side that appears to be diseased most severely is recommended. Contralateral repair is undertaken only when hypertension persists and when repeat functional studies lateralize to the unoperated side.
The clinical significance of plasma renin activity determination.
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Are there unknown mineralocorticoids in low-renin essential hypertension?
The blood pressure elevation of primary aldosteronism is caused by excessive production of the known mineralocorticoid, aldosterone. The blood pressure elevation of low-renin essential hypertension may also be caused by mineralocorticoid excess, but which which mineralocorticoid is responsible is uncertain. Normal levels of aldosterone, found in this disorder despite suppressed plasma renin, and the presence of an unknown mineralocorticoid have been hypothesized to explain low-renin essential hypertension. We contrasted the blood pressure responses and changes in aldosterone seen in patients with low-renin essential hypertension and primary aldosteronism during treatment with two adrenal enzyme inhibitors. The results demonstrate the similarity between decrease in blood pressure and in aldosterone during early adrenal inhibition in both primary aldosteronism and in low-renin essential hypertension. During treatment with a distal adrenal blocker, patients with primary aldosteronism demonstrated decreases in both aldosterone and blood pressure, whereas patients with low-renin essential hypertension showed a decrease in aldosterone without significant change in blood pressure. This suggested that aldosterone was not the major mineralocorticoid responsible for low-renin essential hypertension. Unknown mineralocorticoid excretion decreased (along with blood pressure) during early inhibition but failed to decrease (along with blood pressure) during late inhibition at a time when aldosterone excretion decreased. This suggests that unknown mineralocorticoids play significant roles in the blood pressure elevation of low-renin essential hypertension.
Study of the renal pressor system in experimental coarctation of the abdominal aorta.
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Screening recognition of primary aldosteronism.
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Gram-negative bacillary meningitis therapy. Polyradiculitis following intralumbar aminoglycoside administration.
Gram-negative bacillary meningitis is a serious threat to patients with head trauma or altered immune systems, or those who have had neurosurgical procedures. The aminoglycoside antibiotics administered systemically and into the cerebrospinal fluid (CSF) have proved useful in the treatment of these infections. Intralumbar and parenteral gentamicin sulfate and tobramycin sulfate were administered to an acromegalic woman with Klebsiella meningitis. She had objective evidence of adhesive arachnoiditis and symptoms of polyradiculitis. Cessation of the aminoglycoside administration resulted in symptomatic improvement, and reinstitution of therapy caused a recurrence of neurologic symptoms. Polyradiculitis may be a complication of the intralumbar administration of aminoglycosides.
Proposed mechanisms of propranolol's antihypertensive effect in essential hypertension.
We studied the antihypertensive effect of propranolol alone and in combination with diuretics in 13 patients with high, 18 with normal and nine with low-renin essential hypertension whose blood-pressure response to diuretics was previously established. Propranolol (160 mg daily) significantly lowered mean arterial pressure in high-renin (129 +/- 2.6 to 114 +/- 2.1 mm Hg) and normal-renin (131 +/- 2.7 to 119 +/- 3.5 mm Hg) patients but not in low-renin patients. A positive correlation (r = 0.36, P less than 0.05) between fall in pressure and fall in plasma renin activity occurred at this dose when the whole group was considered. An antihypertensive effect occurred in both high-renin and low-renin hypertension during large-dose (320 to 960 mg daily) propranolol therapy. This effect was independent of changes in plasma renin activity. The antihypertensive effects of propranolol and diuretics were additive in normal-renin and high-renin hypertension. These data suggest that propranolol's pressure-lowering activity is due to both renin-dependent and renin-independent effects.
Metabolism of digitoxin in man and its modification by spironolactone.
The effect of spironolactone on the metabolism of intravenously administered 3H-digitoxin (80 muCi) was investigated in eight patients. In three of them the labelled glycoside was given on a second occasion after spironolactone treatment had been discontinued for at least 65 days. Of total urinary radioactivity 79% was unaltered drug and 12% consisted of water soluble compounds. No digitoxigenin or digoxigenin and only trace amounts (less than 2 %) of digoxin and the bis- and monoglycosides of digoxigenin were found. After spironolactone total urinary radioactivity was unchanged but the fraction eliminated as unchanged digitoxin fell from 79 to 66 % and the water soluble compounds increased from 12 to 26 % (p less than 0.05). In addition spironolactone caused a 20 ( reduction in the half-life of serum radioactivity (p less than 0.01) and a 16 % reduction in the volume of distribution (p less than 0.05). Induction of hepatic enzymes by spironolactone is proposed to explain the alteration in the metabolism of digitoxin in man. Both the altered metabolic pattern and the reduction in the volume of distribution appear to contribute to the reduction in half-life.
Plasma binding and the affinity of propranolol for a beta receptor in man.
The effects of plasma drug binding on the relationship between propranolol concentration and the antagonism of isoproterenol tachycardia have been investigated in 8 normal subjects and 8 hypertensive patients. During chronic intravenous infusion of propranolol giving a narrow range of total plasma concentrations (22.5 to 50 ng/ml), there was, at best, a poor correlation with effects. On the other hand, there was excellent correlation between efficacy and free drug concentration, which fitted the predictions of the receptor theory of competitive antagonism. The true affinity constant for the binding of propranolol to its receptor can be calculated in terms of free drug concentration (KAfree) and was found to vary 2-fold compared to the affinity constant in terms of total plasma concentration (KAtotal) which varied 4-fold, the greater variation being due to plasma binding differences. Compared to normal subjects, KAfree and KAtotal were smaller in hypertensive subjects, implying lesser sensitivity to the drug, and plasma propranolol binding was greater. There was no difference in KAfree between high- and low-renin essential hypertensives, but KAtotal was smaller in the high-renin group due to increased plasma binding which did not reach statistical significance. It is concluded that the effect of propranolol on heart rate is a predictable function of free drug concentration in man and that the contribution of individual variation in receptor sensitivity to differences in oral dosage requirement is minor compared to that of variations in bioavailability.
Renal carcinoma discovered incidentally by arteriography during evaluation for hypertension.
Since June 1, 1971 patients undergoing evaluation for hypertension have been evaluated with rapid sequence excretary urography, abdominal aortography and selective renal arteriography. Renal venous assays have been done in selected patients. Through July 31, 1974, 812 arteriographic studies in new hypertensive patients have been done. In 6 of these patients renal tumors were discovered by arteriography only and were not suggested by symptoms, urinalysis nor diagnosed on hypertensive excretory urography. This high incidence surprised us and we hope others will review their arteriographic series of hypertensive patients.
Failure of aspirin to antagonize the antihypertensive effect of spironolactone in low-renin hypertension.
Aspirin has been shown to acutely block the natriuretic effect of spironolactone in the mineralocorticoid-treated normal rat, dog, and man. It has been suggested that aspirin is contraindicated in hypertensive patients receiving spironolactone. Five patients with low-renin essential hypertension and two with hypertension due to primary aldosteronism, all of whom have normalized their blood pressure on chronic spironolactone therapy, were cotreated in a double-blind fashion with either aspirin or aspirin-placebo during alternate six-week periods. Aspirin did not appear to alter the effect of spironolactone on blood pressure, serum electrolytes, urea nitrogen, or plasma renin activity.
Suppression of plasma renin activity by indomethacin in man.
The effect of indomethacin or placebo on aldosterone, plasma renin activity (PRA), sodium excretion, and urinary prostaglandin (PG) levels was investigated in five hypertensive subjects in 100 mEq sodium balance who had experienced malignant hypertension with a disturbance of their renin-aldosterone relationship in the past. Indomethacin significantly lowered aldosterone levels by 43%, PRA by 58%, 24-hour sodium excretion by 49%, and urinary PG excretion, an indicator of renal PG synthesis, by 67%. Angiotensin infusion increased aldosterone to the same level before and after treatment with indomethacin. Similarly, in normal subjects in 150 mEq sodium balance, indomethacin lowered PRA by 47%; sodium excretion fell by 33%, and urinary prostaglandin E (PGE) excretion, by 55%. The acute elevation in PRA 10 minutes after intravenous furosemide was completely abolished by indomethacin. Five subjects with essential hypertension were classified as normal renin hypertensives according to their response to orally administered furosemide. Indomethacin pretreatment resulted in 60% reduction of PRA following furosemide, and three of these subjects now fell into the low renin category. Studies in vitro demonstrated that indomethacin has no effect on the renin-renin substrate interaction. Thus, indomethacin lowers PRA concomitantly with a reduction in renal PG synthetase activity. Whether indomethacin inhibits renin release by an intrarenal, PG-related mechanism or secondarily via sodium retention is discussed.
Hypertension reviews: the incidence of low-renin essential hypertension in Davidson County, Tennessee hypertensives.
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