Frederick Olmsted

Arterial Hypertension Elicited by Subpressor Amounts of Angiotensin

Long-term infusion of amounts of angiotensin insufficient at the beginning to raise arterial pressure results, after several days in sustained arterial hypertension in unanesthetized dogs. This hypertension is to a large degree dependent on environmental stimuli, and results chiefly from increase in peripheral resistance. As in dogs with renal hypertension, there is increased pressor responsiveness to tyramine. This indirect action of angiotensin to increase total peripheral resistance and arterial pressure by an action on the sympathetic nervous system, along with an upward resetting of the carotid sinus buffering mechanism, might logically account for the neural component of chronic renal hypertension. Such a proposal integrates the humoral and neural elements of the mosaic describing the mechanisms of tissue perfusion.

Serum Lipid Levels in Normal Persons Findings of a Cooperative Study of Lipoproteins and Atherosclerosis

Measurements of Sf 12-20, Sf 20-100, and total serum cholesterol made on 10,690 men and 3,404 women are reported and the relation of lipid level to race, source, age, sex, blood pressure, and weight is described. Distributions for men 40 to 59 are reported in detail. The groups studied, while not selected as representative of the population at large, were remarkably similar in their lipid levels. The lipid levels of only 2 of the 33 groups—Los Angeles and the prisoners—differed significantly from the average. No convincing explanation for either of these exceptions was discovered. The data in this study were mainly from a white population. Data for nonwhites came primarily from 2 aberrant groups and were too meager to allow a clear characterization of lipid levels. The levels for nonwhites from these 2 sources were closer to those of the white members of these groups than to the levels of the general population. Cholesterol levels for men and women were found to be about the same at age 20. For both sexes the level rises with age but at first the rise is much greater for men than women. Above age 50, however, the level is higher for women than men and the level for women continues to rise after that age—at least within the age series for this study. The level for men reaches a peak at age 55, after which it declines. The relation of age and sex with lipid level for Sf 12-20 and Sf 20-100 appeared to be similar to that for cholesterol. Correlations of lipid levels with blood pressure and weight were positive but very low. Hypertension or obesity, however, is associated with some elevation of lipid levels. Sf 20-100 was found to be the most sensitive of the 3 lipid measures to sex and race differences. In the age group 40 to 59 it was the only one that exhibited a definite race and sex differential. In addition, it had the highest correlation with weight and with blood pressure.

Hemodynamic Changes in Trained Dogs During Experimental Renal Hypertension

The hemodynamic events, during onset of experimental renal hypertension, and during its progression to the chronic state, were recorded in 19 trained quiet dogs for 20 to 30 minutes daily for four to forty-two days. This was made possible by implanting a flow probe around the root of the aorta, and a catheter in the aortic arch for connection to an external pressure gauge. Continuous graphic recordings of blood pressure, cardiac output, stroke volume, heart rate, and peripheral resistance were made daily during a period of training to obtain control values, and after hypertension was initiated by partial occlusion of a renal artery and unilateral nephrectomy. The average mean arterial pressure in 34 unanesthetized dogs in this study was 85 mm Hg (range, 68 to 116 mm Hg). This is about 30&%; below values previously reported by others in unanesthetized dogs. These low pressures were ascribed to lack of restraint, to training, and to the natural posture of the dogs. At onset of hypertension a sharp rise in arterial pressure was accompanied by a decrease of cardiac output and heart rate, and by a large abrupt increase of peripheral resistance. After one to four days, the continued rise of arterial pressure was associated with return of cardiac output and heart rate toward normal. Peripheral resistance eventually stabilized at a level above that of the initial large rise. A chronic state of hypertension was reached by ten to twenty days after the initial rise of pressure. At this time cardiac output and heart rate were restored to normal, while peripheral resistance remained elevated. Studies lasting for as long as forty-two days did not show further changes. If the renal arterial constriction was severe, a third, “malignant” phase ensued with extreme elevation of diastolic pressure, reduction of cardiac output, and greatly increased peripheral resistance. This terminated in uremic death after a few days.

Hemodynamic Aspects of Prolonged Infusion of Angiotensin into Unanesthetized Dogs

Arterial pressure, cardiac output, stroke volume, heart rate, and peripheral resistance have been recorded daily in eight trained, healthy dogs with implanted aortic flow probes and aortic catheters. After suitable control periods angiotensin II was infused for periods of from 2 to 29 days. The effects observed were considered under four categories: 1) The immediate effects consisted of rise of arterial pressure, decrease of cardiac output and heart rate, rise of peripheral resistance and increased pulse pressure. Within five days all values tended to return to control levels unless the infusion rate of angiotensin was increased. 2) A chronic phase followed and, during this period, cardiac output was normal while arterial pressure and peripheral resistance were elevated. 3) After infusions were stopped pressure and peripheral resistance rapidly declined to be low normal, while cardiac output and heart rate rose to above normal. 4) A transient “malignant” phase was elicited by very large increases in the rate of angiotensin infusion, during which cardiac output and stroke volume were diminished while arterial pressure and peripheral resistance were increased greatly. The hemodynamic changes resulting from prolonged angiotensin infusion were similar in some respects to those found by us during the onset of hypertension due to renal artery constriction in dogs. They differed, however, in that doses of angiotensin, which were great enough to induce arterial pressure elevations similar to those of chronic experimental renal hypertension, reduced stroke volume, and these higher pressures could not be maintained for more than a few days. Hypertension did not persist after discontinuing angiotensin even after 28 days of almost continuous infusion. There was a distinct tendency for the pressor response to diminish with passage of time; more angiotensin was required to maintain similar elevations of arterial pressure.

Blood Pressure in the Unanesthetized Rat. I

Methods of indirectly determining blood pressure in the rat are reviewed and their drawbacks noted. A new method is described which has the advantage of objectivity and provides permanent graphic record of each determination. The end point used is the reappearance of pulsation in the foot distal to a slowly deflating leg cuff. Application of the method is described and its use compared with tail plethysmography.

Blood Pressure in the Unanesthetized Rat II. Spontaneous Variations and Effect of Heat

Heating is commonly used in indirect determinations of blood pressure in the rat. Its effect on arterial pressure is determined at short sequential intervals by a method which permits rapid measurements. Spontaneous variations in the rats blood pressure are noted and analyzed. A plan is suggested which minimizes the effect of these variations by setting up criteria of significance of blood pressure change as between control and experimental periods.

Phase Detection Electromagnetic Flowmeter-Design and Use

Two types of gated sine-wave electromagnetic flowmeter are examined critically, and found to be sensitive to phase shift in the transducer signal. This phase shift is always found in a sine-wave flow transducer because of imperfection in construction, particularly in those used for physiology and medicine. A flowmeter design that discards amplitude modulation and is sensitive to phase change only is described. Advantages over other types of electromagnetic flowmeter are discussed. Results obtained with the phase detection flowmeter are illustrated.