Nosrat Naftchi

Hypertensive crises in quadriplegic patients. Changes in cardiac output, blood volume, serum dopamine-beta-hydroxylase activity, and arterial prostaglandin PGE2.

The syndrome of autonomic dysreflexia often occurs in quadriplegic subjects and is characterized by paroxysmal hypertension, headache, vasoconstriction below and flushing of the skin above the level of transection, and bradycardia. These attacks may cause hypertensive encephalopathy, cerebral vascular accidents, and death. In five patients during crises, the mean arterial pressure changed from 95 to 154 mm Hg, heart rate 72 to 45 beats/min, cardiac output 4.76 to 4.70 L/min, and peripheral resistance 1650 to 2660 dynes-sec-cm-5. In eight subjects the control plasma, red cell, and total blood volumes were 19.1, 10.5, and 29.6 ml/cm body height, respectively, and when hypertensive, the plasma protein concentration increased by 9.9% and the hematocrit by 9.5%. Plasma volume was only reduced by an estimated 10–15%. At that time, arterial dopamine-hydroxylase (D,H) activity increased 65% and prostaglandin E2 concentration by 68%. Thus, the augmented D#H activity represented primarily an elevated sympathetic tone and not hemoconcentration of that protein. The rise in prostaglandin may contribute to the severe headaches during hypertensive episodes.

The effect of spironolactone on digital vascular reactivity in essential hypertension

Abstract 1. 1. Spironolactone was administered (100 mg. daily) to 16 hypertensive patients for 2 weeks. 2. 2. Brachial and digital blood pressures and digital blood flow (calorimetric) were measured before and after vasodilatation by indirect heat supplemented by ganglion blockade, as well as during the intravenous administration of l-norepinephrine (NE). These measurements were made before and at the end of the drug period and from the data, changes in digital vascular caliber and work of vasoconstriction were calculated. 3. 3. The drug produced a statistically significant decrease in supine brachial and digital blood pressure and in digital vascular reactivity to NE. 4. 4. These decreases seem attributable to sodium depletion by the drug.

The effect of aldosterone on electrolytes and on digital vascular reactivity to I-norepinephrine in normotensive, hypertensive, and hypotensive subjects☆

Abstract 1. 1. Aldosterone was administered intramuscularly to 15 normotensive subjects and 15 patients with essential hypertension who were on a fixed intake of sodium chloride. Two patients with renal hypertension and 2 with postural hypotension were also studied. 2. 2. The excretion of sodium in the urine was significantly decreased in the normotensive group. The other electrolyte changes were inconclusive. 3. 3. Digital vascular responsiveness to 1-norepinephrine was significantly increased from an initially high level by the aldosterone in the subjects with essential hypertension but only slightly increased in the normotensive subjects. It was also found to increase from an initially normal level in the 2 patients with renal hypertension, and to decrease from an initially high level in the 2 patients with postural hypotension. 4. 4. The possible mechanisms involved in these changes are discussed.

The Cause of Essential Hypertension

When the blood-pressure cuff was discovered about sixty years ago, it became apparent to many workers in Europe and in this country (1-4) that high blood pressure was a common affliction ofthe adult human being which not infrequently caused his death, either directly or indirectly. It could cause a blood vessel to burst in the brain, produce progressive deterioration ofthe kidneys, cause the heart to fail, or accelerate the process of arteriosclerosis. Arteriosclerosis, in turn, could lead to vascular occlusions, especially in the heart, brain, or extremities, and so hasten the end. Through the years many causes have been propounded for this disease, including psychic disturbance (5), endocrine imbalance (6), hereditary predisposition (7), neurovascular dysfunction (8) (initiated, for example, by the carotid sinus), renal malfunction (9), etc. When the smoke of controversy had cleared a little, some hypertensive diseases, such as those associated with adrenal medullary tumors (10) and adrenal cortical tumors or hyperplasia (11) and those associated with such renal diseases as acute and chronic glomerulonephritis, chronic pyelonephritis, and polycystic kidneys, were distinguished from primary hypertension itself, although even today this distinction cannot always be made clinically in the individual patient. When neurogenic hypertension was produced in the laboratory by section of the aortic depressor and carotid sinus nerves of dogs (12) and when renal hypertension was produced by interfering with the canine renal arterial circulation (13), opposite schools of thought developed. One identified primary hypertension as essentially renal, the other believed it to be essentially nervous in origin. However, tissue examined directly by biopsy or at autopsy revealed no renal abnormality early in the course of * Department ofMedicine, Mount Sinai Hospital, New York. This work has been aided by grants from the American Heart Association and the National Heart Institute (H-I164).

Digital vascular reactivity to L-norepinephrine in the second trimester of pregnancy as a test for latent essential hypertension and toxemia.

I N 1 9 5 7 1 neurogenic vasoconstriction was estimated quantitatively by measuring blood pressure and blood flow in the digit under standardized conditions of rest and room temperature and again after vasodilatation by indirect heat supplemented by the intravenous injection of a ganglion-blocking drug. These data were converted to radius equivalents by means of PoiseuiIles law ancl from these radius equivalents and the pressures the physical work performed by the smooth muscle of the blood vessels in changing one steady state (vasodilatation) to another (vasoconstriction) was calculated. With these methods, neurogenic vasoconstriction was demonstrated to be increased over normal values in essential hypertension. A similar procedure was subsequently applied to estimating vascular reactivity to L-norepinephrine (NE) by measuring the work of vasoconstriction produced by digital vascular smooth muscle in response to a fixed rate of infusion of NE.2 Such reactivity was found to be strikingly and uniformly increased in essential hypertension.

Reactivity of the digital blood vessels to angiotensin II in normotensive and hypertensive subjects

Abstract 1. 1. Digital vascular reactivity to infused angiotensin II was measured in 15 normotensive subjects and 15 pateints with essential hypertension. 2. 2. This reactivity was found to be increased in the hypertensive group. 3. 3. The mechanisms involved are discussed.

Angiotensin II Studies in Hypertension

1. In primary hypertension, the digital blood vessels are more reactive than normal to angiotensin II as well as to l-norepinephrine. 2. In terms of weight, the potency of angiotensin II in constricting digital blood vessels is 10 times that of norepinephrine in both normotensive and hypertensive subjects. 3. The turnover of angiotensin II-I131 is slower than normal in patients with primary hypertension. 4. Digital vascular reactivity to both l-norepinephrine and angiotensin II is normal in “pure” renal hypertension. 5. Angiotensin II-I131 turnover, in contrast, in the case of renal hypertension studied, was slower than in the normal group and was similar to that in the case of primary hypertension.

Metabolism of Angiotensin II-I131 in Normotensive and Hypertensive Human Subjects

B IOLOGICAL ASSAYS of angiotensin in the blood of patients with normal blood pressures, patients with benign essential hypertension, and patients with malignant hypertension indicate that there are significantly greater quantities of angiotensin in the subjects with benign essential hypertension than in the normotensive group and that the greatest quantities of angiotensin are present in the patients with malignant hypertension. The present investigations were designed to determine the metabolism and rate of turnover of angiotensin in normotensive and hypertensive human subjects.

The Metabolism of Angiotensin II

1. I131-labeled angiotensin II has been employed to study the metabolism of this polypeptide. 2. Following the intravenous administration of angiotensin II-I131 to normotensive and untreated primary benign hypertensive subjects, a slower angiotensin II degradation rate and a larger final volume of distribution of angiotensin II-I131 was found in the hypertensive than in the normotensive patients. The slow rate of degradation of angiotensin II may be responsible for the increased quantity and concentration of this polypeptide in the body fluids. 3. Greater quantities of angiotensin II-I131 are degraded in vitro by sera from untreated primary benign hypertensive patients than from normotensive or secondary renal hypertensive patients. There is evidence for the presence of a serum factor or factors enhancing angiotensin II-I131 degradation and for the presence of a heat labile inhibitor.

Vascular reactivity in the patient with essential hypertension and hypertension of renal origin

Abstract 1. 1. It has been demonstrated that vascular reactivity of the blood vessels of digital skin and forearm muscle to such vasoactive substances as 1-norepinephrine or angiotensin II is increased in primary hypertension. This is best demonstrated after blockade of casual sympathetic nervous activity. In forearm muscle intraarterial infusion is necessary to avoid general reflex effects. In the digit, however, the effect can be demonstrated during the infusion of the vasoactive substance intravenously. 2. 2. Although structural changes occur in primary hypertension, these are probably not responsible for the increased reactivity. Reactivity is normal or only slightly elevated, for example, in renal hypertension and in Raynauds disease in which structural changes in the digital vessels are known to be present. 3. 3. Also, reactivity is increased by glucocorticosteroids in the normotensive but not in the primary hypertensive subject, whereas aldosterone increases reactivity more in the hypertensive than in the normotensive subject. Reactivity is decreased, moreover, by chlorothiazide and its congeners in the primary hypertensive but increased by these drugs, at least in the digit, in the normotensive subject. Increased reactivity, moreover, develops very early in the course of primary hypertension and can be demonstrated in the children of hypertensive patients prior to any elevation of blood pressure. 4. 4. These phenomena therefore probably have a chemical cause the exact nature of which is unclear. A decrease in the turnover of angiotensin II has been demonstrated in primary hypertension, but no such change has as yet been indicated for norepinephrine. Evaluation of the binding and metabolism of these substances in hypertension is necessary. The chemical defect may reside here or in smooth muscle metabolism itself and is probably the factor which is transmitted through the germ plasm and which initiates essential hypertension.