Hollis D. Kleinert

Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the renin-aldosterone system in dogs

Auriculin is a potent vasoactive and natriuretic peptide that was recently isolated and purified from rat atrial tissue. Since this peptide could be of great importance for renal, cardiovascular, and volume homeostasis, its functional properties have been characterized in dogs. The effects of synthetic auriculin on renal function, mean blood pressure, plasma renin activity, renin secretory rate, and plasma aldosterone levels were determined. Auriculin was administered intravenously as a prime (1.0 microgram/kg body weight) and constant infusion (0.1 microgram per minute/kg body weight for one hour) to five anesthetized dogs. In addition, two conscious dogs were used to verify some of the results obtained in anesthetized dogs. Auriculin decreased mean blood pressure from 134 +/- 5 to 122 +/- 4 mm Hg (p less than 0.05, paired t test) and increased glomerular filtration rate (25.5 +/- 2.7 to 32.4 +/- 4.1 ml per minute per kidney, p less than 0.05), diuresis (0.21 +/- 0.03 to 1.06 +/- 0.14 ml per minute per kidney, p less than 0.05), natriuresis (38 +/- 0.6 to 187 +/- 35 mueq per minute per kidney, p less than 0.05), and kaliuresis (14.8 +/- 1.6 to 35.7 +/- 6.3 mueq per minute per kidney, p less than 0.05). These effects were sustained throughout the infusion of auriculin and were entirely reversible. Renal plasma flow increased transiently for one to two minutes, and then returned to or below control levels. Urine osmolality decreased by 40 percent (p less than 0.05) whereas free water clearance remained unchanged (p less than 0.05). Auriculin reversibly decreased plasma renin activity (11.6 +/- 2.3 to 3.6 +/- 1.2 ng/ml per hour, p less than 0.05), renin secretory rate (895 +/- 313 to 255 +/- 28 ng per hour per minute, p less than 0.05), and plasma aldosterone levels (8.4 +/- 1.6 to 3.6 +/- 0.7 ng/dl, p less than 0.05), whereas plasma cortisol levels remained unchanged. These results demonstrate that auriculin has a unique combination of functional properties, increasing glomerular filtration rate, diuresis, and natriuresis, without a sustained increase in total renal blood flow, and lowering blood pressure, plasma renin levels, renin secretory rate, and plasma aldosterone levels. These properties suggest an important potential role for atrial natriuretic peptides in the regulation of renal function, extracellular volume, and blood pressure.

What is the value of home blood pressure measurement in patients with mild hypertension

To investigate the value of home blood pressure (BP) measurements, the BP was recorded daily by the patient at home and compared with recordings in the physicians office and with a 24-hour BP recording taken with a noninvasive ambulatory BP recorder in a group of 93 patients with mild untreated hypertension. Office BPs (mean 148/94 mm Hg) were higher than either home (138/89 mm Hg) or average 24-hour BPs (131/89 mm Hg). For systolic BP, home and office measurements gave similar correlations with 24-hour BP (0.67 and 0.55). For diastolic BP, however, home readings were lower and more accurate (0.76 vs 0.36). Thus, our findings indicate that home readings reflect the overall level of BP more reliably than office readings, and if due consideration is given to the fact that they are usually lower than office readings, they may be used as an alternative and cost-effective means of evaluating patients with mild hypertension.

Situational variations of blood pressure in ambulatory hypertensive patients.

&NA; Blood pressure and heart rate were recorded at 15‐min intervals for 24 hr in 60 untreated patients with uncomplicated mild essential hypertension using a new automatic noninvasive portable recorder. During the recording, the patients went about their normal daily routine, of which they kept a detailed record. The data were analyzed for five different recording situations: in the clinic, at work, at home, asleep, and average of the entire 24‐hr period. Twenty‐four hour readings were also compared with previously obtained casual readings. Clinic readings were correlated with the average 24‐hr values, but for individual patients clinic pressures were relatively poor predictors of 24‐hr pressures. Pressures recorded in the clinic were also greater than average 24‐hr values. Similar degrees of correlation were found between clinic, home, work, and sleep pressures. Pressures recorded in the clinic were similar to pressures at work but higher than at home or asleep. In contrast, heart rate was similar in all conditions except during sleep, when it was lower. Previously measured casual pressures were also correlated with the clinic readings, with systolic values being similar, but diastolic values higher in the clinic during the 24‐hr recording. For patients with clinic diastolic pressures in the range 90‐104 mm Hg, 24‐hr pressures varied from 75 to 100 mm Hg. We conclude that pressures measured casually in the clinic do not accurately reflect average 24‐hr pressures and that ambulatory recording is helpful in the evaluation of mildly hypertensive patients.

Cardiovascular effects of atrial natriuretic factor in anesthetized and conscious dogs.

Atrial natriuretic factor lowers blood pressure in normotensive and hypertensive animal models. The present study examined the mechanism of the blood pressure-lowering effect in 10 normotensive dogs. Four awake dogs previously instrumented with electromagnetic flow probes for measurement of cardiac output and catheters for systemic hemodynamic and cardiac dynamic measurements were studied. After a 30-minute control period, a 3 micrograms/kg bolus followed by 0.3 micrograms/min/kg of a 24-residue synthetic atrial natriuretic factor was infused for 30 minutes, followed by a 1-hour recovery period. Mean arterial pressure fell significantly during infusion (control, 125 +/- 4; infusion, 108 +/- 5; recovery, 125 +/- 9 mm Hg; p less than 0.05) and was accompanied by a slight but significant bradycardia (control, 144 +/- 7; infusion, 134 +/- 5; recovery, 145 +/- 7 beats/min; p less than 0.05). Significant reductions in cardiac output (control, 2.66 +/- 0.60; infusion, 2.18 +/- 0.60; recovery, 2.74 +/- 0.60 L/min; p less than 0.05), stroke volume (control, 18.4 +/- 3.9; infusion, 16.0 +/- 4.2; recovery, 19.0 +/- 3.7 ml/beat; p less than 0.05), and maximum increase in rate of change of left ventricular systolic pressure (control, 2475 +/- 200; infusion, 2088 +/- 216; recovery, 2487 +/- 243 mm Hg/sec; p less than 0.05) were also observed during infusion. No significant changes in total peripheral resistance or central venous pressure were noted, although the latter tended to fall during infusion. A similar pattern was observed in six pentobarbital-anesthetized dogs, except that infusion of atrial natriuretic factor did not induce bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Monitoring in the Evaluation of Blood Pressure in Patients with Borderline Hypertension and the Role of the Defense Reflex

The differences between blood pressure (BP) readings taken in the clinic and during normal daily activities were assessed in two studies using a noninvasive ambulatory BP monitor (Avionics). In the first study 30 untreated hypertensive patients (17 with borderline pressures, average diastolic less than or equal to 95, and 13 established hypertensives, diastolics above 95) and 5 normotensive subjects had 30 readings taken in the physicians office and 30 while at home. Conventional sphygmomanometer BPs were also recorded in the office. In the borderline group home BPs were significantly lower than clinic BPs, whereas this difference was less marked for the established and normotensive group. In the second study BP was measured every 15 minutes for 24 hours in 25 normal subjects, 25 borderline and 25 established hypertensives, and readings categorized according to four recording situations: physicians office, work, at home, and sleep. BPs in all groups were highest at work and lowest asleep, and directional changes were similar. Both hypertensive groups showed higher BPs in the physicians office than at home, while normal subjects showed no difference. BPs recorded in the physicians office were good predictors of 24 hour average BP in normal and established hypertensive subjects, but not in the borderline group: in such patients 24 hour monitoring may be of particular value in evaluating the need for treatment.

Comparable effect of isotonic infusions on blood pressure in the anephric rat.

Whether and to what extent sodium chloride infusions elevate blood pressure acutely were examined in conscious, normotensive, and spontaneously hypertensive (SHR) anephric rats. All animals were bilaterally nephrectomized 18 hours before study. Normotensive Wistar rats, allowed no food or water post nephrectomy (Groups I-IV), received either no infusion (Group I, control) or intravenous infusion of isotonic solutions of either NaCI, mannitol, or dextrose at a rate of 0.018 ml/min for 2 hours. Mean arterial pressure (MAP) measurements were determined directly by arterial catheter for control (C), 1 hour, and 2 hours. Blood pressure was increased above control in all groups at 1 hour and 2 hours (p < 0.05). The increase in MAP with NaCI was similar to that with no infusion or infusion of mannitol or dextrose. Normotensive Wistar rats (Groups V-VI) and SHR (Group VII) were allowed free access to food and water post nephrectomy and received either no infusion (Group V, control) or infusion of isotonic saline at a rate of 0.037 ml/min for 2 hours. MAP was elevated above control in all groups (V-VII) at 1 and 2 hours (p < 0.05). The magnitude of the rise was similar among all groups. Food and water accessibility post nephrectomy did not alter results. In both sets of experiments when saline was infused we were unable to identify any increase in blood pressure greater than control at either infusion rate. In fact, we continued the saline infusion in Group VI, until 100 ml of saline was infused without any elevation in blood pressure above control. We conclude that during the 2 hours of observations neither sodium nor chloride ions exert an independent eifect on MAP in normotensive or hypertensive anephric rats when compared to no infusion or isotonic isovolemic infusions of mannitol or dextrose during the same time period. (Hypertension 5: 421-426, 1983)