Effect of dietary potassium on blood pressure, renal function, muscle sympathetic nerve activity, and forearm vascular resistance and flow in normotensive and borderline hypertensive humans.

We evaluated the effect of a low potassium diet on blood pressure in normotensive (NT) and in borderline hypertensive subjects (BHT). There were 11 BHT men (age, 24.6 +/- 1.2 years) and 10 NT men (age, 23.5 +/- 1.0 years). Subjects were studied while on both low potassium, high sodium (30 meq/day, 400 meq/day) diets and high potassium, high sodium (100 meq/day, 400 meq/day) diets, each taken for 6 days. During the low potassium diet, daytime ambulatory systolic blood pressure increased in both NT (123 +/- 5 mm Hg, low potassium, vs. 116 +/- 4 mm Hg, high potassium, p less than 0.01) and BHT groups (134 +/- 3, low potassium, vs. 124 +/- 3, high potassium, p less than 0.001). Mean blood pressure was not different in NT during the two diets but was significantly higher during the low potassium diet in BHT subjects (97 +/- 2 mm Hg low potassium, vs. 92 +/- 1 mm Hg, high potassium, p less than 0.05) without change in heart rate in BHT subjects during the two diets. Low potassium diet increased the postural rise in diastolic blood pressure when subjects changed from the supine position to quiet standing (standing diastolic blood pressure for NT: low potassium, 79 +/- 2 mm Hg vs. high potassium, 72 +/- 2 mm Hg; for BHT: low potassium, 89 +/- 2 mm Hg vs. high potassium diet, 83 +/- 2 mm Hg, p less than 0.01). The effects of low potassium diet on blood pressure were not related to marked changes in renal hemodynamics, in plasma renin activity, in aldosterone, or in norepinephrine, nor to increases in forearm vascular resistance or in muscle sympathetic nerve activity. In fact, muscle sympathetic nerve activity decreased in the BHT group during low potassium compared with high potassium diets (p less than 0.001) and did not change in the NT group. Sympathetic nerve activity was also higher in BHT compared with the NT group during high potassium and low potassium diets, p less than 0.001. In the NT group, the low potassium diet was associated with lower hematocrit levels, weight gain, and increased 24 hour urinary calcium levels. After the low potassium diet, serum potassium fell in both groups, and serum phosphorus fell significantly in the BHT group.(ABSTRACT TRUNCATED AT 400 WORDS)

Dietary salt produces abnormal renal vasoconstrictor responses to upright posture in borderline hypertensive subjects.

We studied the effect of high and low NaCl diets in normotensive and borderline hypertensive subjects to determine if a high NaCl diet produces abnormal renal vasoconstriction during the stress of upright posture in borderline hypertensive subjects. We studied 13 normotensive young men with diastolic blood pressures below 85 mm Hg and nine borderline hypertensive young men defined by diastolic blood pressures intermittently above 90 mm Hg. The subjects achieved comparable sodium balance during 6 days of low NaCl (10 mEq Na, 40 mEq Cl, 100 mEq K) and high NaCl (400 mEq Na, 400 mEq Cl, 100 mEq K) diets. In the normotensive subjects, standing for 30 minutes resulted in a tendency for diastolic blood pressure to fall during both diets. In contrast, during standing borderline hypertensive subjects showed no change in diastolic blood pressure during the low salt diet and a tendency for diastolic blood pressure to increase after the high salt diet. Standing reduced renal plasma flow in both groups during both diets. However, only during the high NaCl diet did the absolute decrease and percent decrease in renal plasma flow during standing differ significantly (p less than 0.05 and p less than 0.01, respectively) between the borderline hypertensive (-151 +/- 24 ml/min/1.73m2; -29 +/- 4%) and normotensive subjects (-79 +/- 17 ml/min/1.73m2; -15 +/- 3%). The resultant increase in the renal vascular resistance index with standing did not differ between the two groups during the low NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Can dropout and other noncompliance be minimized in a clinical trial? Report from the Veterans Administrative National Heart, Lung and Blood Institute cooperative study on antihypertensive therapy: mild hypertension.

Long-term clinical trials must face the problem of participants who drop out before the study is closed or who in other ways do not comply with the protocol. In a joint Veterans Administration-National Heart, Lung and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups and followed for up to 30 months. The data were analyzed for factors related to dropout and to medication and visit noncompliance. Large differences in dropout and compliance rates were found by clinic and age but not by treatment allocations (active vs. placebo) nor race-sex. In addition, noncompliance was 78%-118% higher in participants who subsequently chose to drop out of the study. Indications were that the attitude of a clinic towards participant complaints, willingness to temporarily reduce medication and vigorous pursuit of those who failed to keep appointments were important factors in reducing dropout. Strategies for minimizing dropout and noncompliance must be part of the study protocol, clinic personnel should be trained in using such strategies, and both clinic and participant compliance should be centrally monitored.

Long-term treatment of Hypertension with methyldopa. II. Therapeutic efficacy.

Efficacy and dosage data were analyzed for patients who received methyldopa up to 4.5 years. A prompt initial response to methyldopa was observed, and the blood pressure reduction was maintained throughout the follow-up period. Mean dosage rose modestly during this time.

Abnormal urinary kallikrein in hypertension is not related to aldosterone or plasma renin activity.

The relationships between urinary kallikrein (Ukal), and plasma renin activity (PRA), urinary aldosterone (Ualdo), Na+ balance, SK+, and renal function were studied in essential hypertensives (EHT) and normals. Ukal was measured by a radiochemical esterolytic assay. We studied 18 white patients with EHT (15 men, 3 women) ages 31.6 to +/- 2.1 (SEM) yrs, BP 138 +/- 2/95 +/- 2 mm Hg. and 12 white normals (NLS) (7 men, 5 women) ages 30.2 +/- 2.3 yrs, BP 112 +/- 4/71 +/- 2 mm Hg. All received a 5-day diet of 400 mEq Na+, 80 mEq K+/day, and 5 days of 10 mEq Na+, 80 mEq K+/day. All achieved Na+ balance by Day 5. On Day 5 of the low Na+ diet, 24 hr. Ukal in EHT was 15.8 +/- 2.4 (esterase units/24 hr) vs NLS, 17.0 +/- 2.8 PRA was the same in EHT and NLS, but Ualdo was higher in NLS. (Day 5, low Na+, EHT, Ualdo = 29.4 +/0 3.3 microgram/24h. vs NLS 41.8 +/- 4.7, p less than 0.02). Analysis of individuals showed that all NLS increased Ukal after salt restriction, while 3 EHT decreased Ukal after salt restriction. This abnormal response in EHT was not related to abnormalities in Ualdo, PRA, Na+ balance, SK+, or creatinine clearance. In 3 EHT with low-renin EHT, the Ukal response was normal. In two of four patients with primary aldosteronism, Ukal was normal despite increased Ualdo. The Ukal response to salt restriction is abnormal in some EHT, unrelated to Ualdo or PRA, suggesting either a primary defect in Ukal and/or the presence of other factors modulating Ukal in EHT.

Serum lipoprotein levels during chlorthalidone therapy. A Veterans Administration-National Heart, Lung, and Blood Institute cooperative study on antihypertensive therapy: mild hypertension.

In a joint Veterans Administration-National Heart, Lung, and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age and with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups. Subjects in the active group received chlorthalidone or chlorthalidone plus reserpine, while the other subjects received matching placebo tablets. After one year of treatment, the chlorthalidone group had increases of 10.0 +/- 1.8 (SE) mg/dL in total cholesterol level, 9.8 +/- 5.2 mg/dL in triglyceride level, and 12.6 +/- 3.4 mg/dL in low-density lipoprotein-cholesterol level above the changes in the placebo group. There was no difference in high-density lipoprotein changes between the two groups (0.1 +/- 0.8 mg/dL). The possible net effect on risk of increasing lipid values while lowering pressure in the long-term treatment of mild hypertension with thiazides or related diuretics must be further evaluated.

Influence of low- and high-pressure baroreceptors on plasma renin activity in humans.

We evaluated effects of the low- and high-pressure baroreceptors on plasma renin activity (immunoassay) using graded lower body suction (LBS) in six healthy men. LBS at -10 and -20 mmHg for 10 min decreased central venous pressure without changing arterial pressure and thereby presumably reduced low- but not high-pressure baroreceptor inhibition of renin release. LBS at these levels produced forearm vasoconstriction, but did not increase renin. LBS at -40 mmHg decreased central venous and arterial pulse pressure and thus reduced both low- and high-pressure baroreceptor inhibition. LBS at this level produced forearm vasoconstriction and tachycardia and increased renin from 2.1 +/- 0.4 (mean +/- SE to 7.4 +/- 1.4 ng.ml-1.h-1 (P less than 0.05). In summary, reduction in low-pressure baroreceptor inhibition in humans did not increase renin in the presence of physiological tonic inhibition from high-pressure baroreceptors. Increases in renin did not occur until there was combined reduction of high- and low-pressure baroreceptor inhibition on plasma renin activity.

Urinary kallikrein in normal renin essential hypertension.

The relationship between urinary kallikrein, urinary aldosterone, and plasma renin activity (PRA) was studied in hypertensive patients and normal subjects. Kallikrein was measured by a radiochemical esterolytic assay. Nine white males with normal renin, mild essential hypertension (25 +/- 5 [SD] yr; blood pressure [BP] 143 +/- 7 / 95 +/- 5 mm Hg) and six white normal males (23 +/- 3 yr; BP 115 +/- 15 / 70 +/- 6 mm Hg) were placed on a one-week diet consisting of 400 mEq Na+, 80 mEq K+ diet and a one week diet of a 10 mEq Na+, 80 mEq K+ diet. During salt restriction, PRA, urinary aldosterone, and urinary kallikrein progressively rose. (Urinary kallikrein on day 7: normals 18.3 +/- 13.7 esterase units [EU] per 24 hr; hypertensives 22.7 +/- 12.5 EU/24 hrs). There were no significant differences between the normals and hypertensives in PRA, aldosterone, or kallikrein excretion. After sodium balance was achieved, during salt loading, the PRA, aldosterone and kallikrein values were similar in both normals and hypertensives. (Urinary kallikrein on day 7: normals 5.0 +/- 5.2; hypertensives 7.9 +/- 4.4 EU/24 hrs.) Abnormalities in urinary kallikrein in hypertensives were not found when young white males with normal renin essential hypertension were compared to age-matched white male normal subjects. PRA appears related to urinary kallikrein excretion in this type of patient.

Effects of high and low sodium intake on arterial pressure and forearm vasular resistance in borderline hypertension. A preliminary report.

The purpose of this study was to evaluate effects of high and low sodium intake on arterial pressure and forearm vascular resistance in subjects with borderline hypertension and to compare responses to sodium excess in these subjects with responses in a recent study in normotensive subjects. Six subjects with borderline hypertension were studied after ten days of high (410 mEq/24hr) and low (10mEq/24hr) sodium intake. Potassium intake was constant. In five of six subjects, high sodium intake decreased forearm blood flow and increased forearm vascular resistance and arterial pressure. During low and high sodium intake forearm blood flow averaged 7.8 plus or minus 1.2 (SE) and 5.9 plus or minus 0.8 ml/min x 100 ml, respectively; forearm vascular resistance averaged 13.5 plus or minus 2.2 and 19.1 plus or minus 3.0 units, respectively; and mean arterial pressure averaged 89 plus or minus 3 and 98 plus or minus 2 mm Hg, respectively. High sodium intake augmented forearm vasoconstrictor responses to lower body negative pressure, a stimulus to neurogenic vasoconstriction. The results contrast with our earlier results in normotensive subjects in whom sodium excess produced forearm vasodilatation and failed to increase arterial pressure significantly. Decreases in renin and aldosterone with high sodium intake were similar in the two groups. The results suggest that excessive sodium intake in subjects with borderline hypertension produces abnormal increases in forearm vascular resistance, neurogenic vasoconstriction, and arterial pressure. The reasons for the contrast between the borderline hypertensives and normotensives are unknown, but they do not seem to be related to the renin-angiotensin-aldosterone system.