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Introduction: This study was done to ascertain the effect of race on medical student-patient communication. The primary hypothesis was that interviewing performance scores would be higher when race of student and race of simulated patient instructor (SPI) were concordant than when they were discordant., Methods: Data obtained from student interactions with four Caucasian and four African American female SPIs participating in a case involving an AIDS risk assessment interview were analysed. Performance was assessed using two instruments: an 8-item behaviourally anchored interviewing skills scale and a 14-item checklist reflecting content relevant to sexual behaviour and AIDS risk. SPI groups were comparable and SPIs were trained to a high level of inter-rater reliability. Students (24 African American and 180 non-African American) were assigned to SPIs based on the spelling of the student's name. Performance was scored independently at the conclusion of each interview by both the SPI and the student her/himself., Results: African American students had lower scale scores than non-African American students in interactions with Caucasian (but not African American) SPIs; and all student scores, both on the skills scale and the content checklist, were higher with African American than with Caucasian SPIs (as assessed by both SPI and student). Women students had higher scores than men., Conclusions: Race of SPI has an influence on student performance of an AIDS risk assessment interview. Further studies focusing on racial interactions in the medical interview are required. It appears that race of SPI may need to be accounted for in the development and interpretation of SPI-based clinical competence exams.

The process whereby a physician explains to the ill patient what has gone wrong and what can be done about it can be taught and evaluated by simulated patients (SPIs). This study was designed to determine whether a training experience in educating a diabetic SPI improves subsequent performance with a hypertensive SPI. Competence in educating a hypertensive SPI by students who had no prior training experience (n = 26) was compared to that of an experimental group (n = 20) that had a prior training session. Performance was assessed with a counseling skills scale and a case-specific content checklist (1 = poor to 5 = excellent). Students in the experimental group performed better than controls in both counseling skills (4.46 v 3.86, P < .01) and completeness of coverage of content (3.28 v 2.65, P < .01). Students in both groups focused more on clinical features and treatment than on laboratory testing and follow-up. The ability to counsel "patients" with hypertension can be enhanced by a prior learning experience with a diabetic SPI. Clinical application of knowledge about hypertension can be assessed by SPIs.

Objective: Our objective was to evaluate the effectiveness of using simulated patient instructors and the Ockene method to instruct third-year medical students in smoking-cessation counseling techniques., Design: We used a clinical exercise with self-study preparation and simulated patient instructors., Methods: One hundred fifty-nine students participated in a smoking-cessation counseling session in which cognitive and behavioral endpoints were assessed by simulated patient instructors and the students themselves., Results: Student performance in the cognitive and behavioral components of model smoking-cessation counseling was acceptable. Specific areas of weakness, such as the tendency of students to underemphasize the personal and social benefits of smoking cessation, and to overestimate their competence on a number of skill items, were identified. Student evaluation of the exercise was positive., Conclusions: Smoking-cessation counseling can be taught effectively to third-year medical students by simulated patient instructors during a clinical clerkship.

Background: Standardized patient instruction (SPI) is recommended as a nonthreatening method for teaching the male genitorectal examination. The article's purpose is to describe the method's effectiveness in reducing anxiety and increasing confidence among men and women students from diverse cultures., Description: We implemented an SPI program in 1993 to teach the examination to 2nd-year students. Students performed their examinations in mixed gender groups of three; a man student was responsible for disrobing the SPI and performing the first exam. During the 45-min session, each of the three students performed the examination in turn, and each received immediate feedback on their technique and interpersonal approach to the patient., Evaluation: All students (n = 190) evaluated their SPI encounter immediately after the session had ended., Conclusions: Men and women students from all ethnic groups reported decreased anxiety and increased confidence levels after the SPI session. These findings indicate that a carefully orchestrated SPI session is effective in reducing students' anxiety about crossing personal space boundaries, overcoming a variety of proscriptions on gender-appropriate interactions, and increasing their confidence to perform this sensitive examination.

We investigated the effect of raising arterial plasma epinephrine within the lower pathophysiological concentration range on various indicators of blood platelet function and hematocrit. Epinephrine was raised over 60 minutes by a stepwise increasing intravenous infusion in 40 healthy men aged 20 to 40 years. Platelet count increased progressively with increasing arterial epinephrine to a maximal change of 69 +/- 6 x 10(9)/L in EDTA-anticoagulated blood and a maximal change of 42 +/- 6 x 10(9)/L in acid-citrate-dextrose (ACD)-anticoagulated blood, and the weight of circulating platelets increased by 29% (P < .001). Platelet size increased significantly in EDTA and decreased in ACD, and the difference between EDTA and ACD was significant (P < .0001) for both count and size, suggesting that epinephrine not only recruits platelets into the circulation but also induces some microaggregation in vivo or adhesion ex vivo. Aggregation of platelets in vitro induced by epinephrine decreased (P < .003 for delta optical density and P = .038 for maximal optical density) after epinephrine infusion compared with saline but did not change when stimulated with ADP or collagen. These findings suggest a selective downregulation of the epinephrine-activating mechanisms concomitant with a rise in the platelet content of epinephrine by 81% (P < .001) and no change in the platelet sodium-proton membrane exchange. The release of granular content (beta-thromboglobulin and platelet factor 4) to the circulation in response to epinephrine was not significant. Thus, under acute conditions it seems that the platelets may protect themselves against inappropriate overstimulation by epinephrine. The importance of platelet epinephrine uptake is still unknown, but sodium-proton exchange does not seem to be involved in regulating the effects of circulating epinephrine on platelet function. Epinephrine has a pronounced effect on raising hematocrit (maximal change of 1.74 +/- 0.13 x 10(-2), P < .0001).

Platelet catecholamine content may reflect integrated plasma catecholamine concentrations over time. The present study aimed at examining sympathetic nervous system (SNS) involvement in essential hypertension by assessing platelet noradrenaline (NA) and typically beta-adrenoreceptor mediated responses to adrenaline (A) infusion as indices of sympathetic tone. Healthy white men were recruited by public advertising and screening (mean +/- SD): Hypertensives (n = 13, sitting blood pressure [BP] 153 +/- 13/106 +/- 7 mmHg, age 34 +/- 5 years, weight 83 +/- 10 kg) were compared to normotensives (n = 13, sitting BP 114 +/- 9/75 +/- 9 mmHg, age 30 +/- 6 years [n.s.], weight 82 +/- 9 kg [n.s.]). Loss of platelet granular contents (including NA) prior to analysis was minimized by studying young subjects (age range 20-40 years, minimal atherosclerosis), using arterial blood sampling, and processing blood immediately. These procedures resulted in plasma beta-thromboglobulin and platelet factor 4 levels which were not significantly different between groups. Sympathetic activation resulting from stress was minimized by not labelling subjects as either hypertensive or normotensive. Mean arterial platelet NA content was significantly higher in hypertensives (64 +/- 31 pg/mg of platelet weight) compared to normotensives (43 +/- 20 pg/mg, p < 0.05) both at baseline and following 35% expansion of the circulating platelet pool by A infusion (p < 0.05) and correlated with arterial NA in the hypertensives (r = 0.79, p < 0.002) but not in the normotensives (r = 0.04, n.s.). Similar increases in platelet and plasma A during infusion in both groups suggest unchanged platelet uptake capacity and plasma clearance in the hypertensive group.(ABSTRACT TRUNCATED AT 250 WORDS)

The hypotensive action of ketanserin in humans remains incompletely defined but may be mediated by factors unrelated to vascular alpha 1 or serotonin2-receptor blockade. We examined the effects of ketanserin on indices of sympathetic drive, alpha 1- and serotonin2-receptor responses, and sympathetic tone in 13 elderly men with mild hypertension. Studies were performed after ten days and six weeks of double-blind assignment to placebo and ketanserin 40 mg twice daily. An eight week long single-blind, placebo washout period separated the double-blind phases. In the entire group, ketanserin lowered BP and heart rate significantly after six weeks but not at ten days. In contrast, plasma noradrenaline, an index of sympathetic drive, and platelet aggregation in response to 1 microM serotonin, an index of serotonin2-receptor antagonism, declined significantly after both ten days and six weeks (P < 0.05) on ketanserin versus placebo. Mean BP after six weeks on ketanserin fell to > 10% in seven patients (responders) and to < 10% in six subjects (nonresponders). Responders had higher baseline SBPs and heart rates compared with nonresponders. Even in responders, BP was reduced at six weeks but not after ten days on ketanserin versus placebo. Plasma and platelet noradrenaline, plasma renin activity, and platelet responses to serotonin at baseline and during ketanserin did not distinguish between responders and nonresponders. Ketanserin reduces sympathetic drive and antagonizes serotonin2-receptors in the short term. The relationship of these actions to the hypotensive effect of ketanserin, which is delayed and dependent on the initial BP, is unclear.

Home blood pressure (BP) monitoring is useful in the clinical management of patients with hypertension and the identification of those with "white-coat" hypertension; i.e. high readings in the clinic but normal BP at home. In the process of evaluating this technique, we compared self-measured home BP with intra-arterial BP. Healthy white men (n = 40) of 20-40 years of age and body weight below 95 kg were recruited by advertising in the local newspaper. Following a standardized procedure, performed within 2-4 weeks of a response to the advertisement, BP was measured by a physician at a clinic screening, by the subject at home (14 readings in 7 days) and finally in the clinic concomitantly intra-arterially and oscillometrically. The correlation coefficient for mean (M) home BP (r = 0.73) and oscillometric BP (r = 0.74) against intra-arterial BP were slightly higher than for screening BP (r = 0.65). However, in plots of the differences for individual MBP between the methods against the average of the methods, it appears that at levels of average MBP above 100 mmHg, screening BP overestimates the BP level, while this was not the case for home BP or oscillometric BP. Thus, by using intra-arterial measurement as standard of comparison, subject self-measured home BP is a reliable method of estimating blood pressure level in young men. Home BP measured shortly after screening and recruitment provides useful information of resting BP in subjects who potentially may have initial anxiety about BP measurement.

Hypercholesterolemia frequently accompanies hypertension, and it has been suggested that by affecting membrane lipid composition, hypercholesterolemia may cause or accentuate abnormalities in several red blood cell transports associated with hypertension. Such an effect might obfuscate the relation of membrane markers to hypertension and decrease their usefulness in genetic studies of the heritable basis of hypertension. To determine if changing plasma lipids affects membrane transport, we studied the effects of the cholesterol-lowering agent lovastatin on red blood cell lithium-sodium countertransport and sodium-potassium-chloride cotransport, red blood cell sodium and water content, and platelet amiloride-sensitive volume responsiveness to cytoplasmic acidification, an indirect measure of sodium-proton exchange that has been proposed as a new membrane marker for hypertension. In a 24-week, placebo-controlled, double-blinded, randomized trial, lovastatin significantly lowered total and low density lipoprotein cholesterol and raised high density lipoprotein cholesterol. Red blood cell lithium-sodium countertransport and sodium-potassium-chloride cotransport were not significantly altered. Red blood cell sodium content decreased significantly in the lovastatin-treated group, probably as a result of an increase in red blood cell sodium-potassium pump activity. Platelet amiloride-sensitive responses to cytoplasmic acidification were significantly depressed by lovastatin treatment, suggesting that lowering plasma cholesterol may suppress platelet sodium-proton exchange. It has been hypothesized that the hyperlipidemias frequently observed in essential hypertensive patients may alter membrane lipid composition and affect membrane cation transport activities.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of various antihypertensive medications on platelet function is of increasing interest. Conflicting effects of captopril on platelet function are reported and the impact of angiotensin converting enzyme (ACE) inhibitors not containing a sulfhydryl group such as enalapril, lisinopril, and quinapril on platelet function remains unstudied. Therefore, the aim of the present study was to examine the effect of antihypertensive treatment with quinapril, a novel ACE inhibitor not containing a sulfhydryl group, on platelet function. Ten white men (age range of 32-61 years) with untreated mild-to-moderate essential hypertension (supine diastolic blood pressure greater than 95 mm Hg) were treated with 4 weeks each of placebo and quinapril in a double-blind, randomized, crossover design. Quinapril (20 mg twice a day) significantly lowered systolic (p less than 0.01) and diastolic blood pressure (p less than 0.01) without any significant effect on heart rate or plasma catecholamines. No significant change was noted for in vitro platelet aggregation induced by epinephrine, ADP, or collagen. Plasma concentrations of the platelet release factors beta-thromboglobulin and platelet factor 4 did not change, nor did the platelet content of norepinephrine, platelet weight (mg/10 ml of blood), circulating platelet count, or platelet size. Thus, as assessed by a broad spectrum of platelet parameters, we found that antihypertensive treatment with quinapril has no significant effect on platelet function in patients with mild-to-moderate essential hypertension. These "platelet-neutral" properties of quinapril suggest that quinapril, both from a thromboembolic and a hemostatic point of view, may be a rather safe agent for treatment of hypertension.

Objective: To determine the relative importance of factors known to cause therapy-resistant hypertension, and to derive an efficient approach to the evaluation of this problem in clinical practice., Design: Consecutive sample., Setting: University hospital hypertension clinic and clinical research center., Patients: Fifteen patients referred for management of refractory hypertension and found to have a seated diastolic blood pressure greater than 95 mm Hg while taking a standard dose of hydrochlorothiazide, propranolol, and hydralazine or its equivalent for at least 4 weeks., Measurements and Main Results: Seven patients (group 1) had normal, resting mean intra-arterial blood pressure (mean pressure less than 107 mm Hg) and eight had elevated pressure (group 2). Patients in group 1 had minimal or not target organ involvement whereas those in group 2 had higher minimum vascular resistance by forearm plethysmography and greater interventricular septal wall thickness. Factors contributing to resistant hypertension, particularly in group 1, were "office hypertension" (clinic systolic blood pressure at least 20 mm Hg higher than home systolic blood pressure), pseudohypertension (cuff diastolic blood pressure at least 15 mm Hg higher than simultaneously determined intra-arterial pressure), and "cuff-inflation hypertension" (intra-arterial diastolic blood pressure rise of at least 15 mm Hg during cuff inflation)., Conclusion: Home blood pressure monitoring and echocardiography are recommended as initial steps in the evaluation of patients with resistant hypertension. Intra-arterial blood pressure measurement is particularly helpful in patients with resistant hypertension who do not have office hypertension yet have normal septal thickness on echocardiography.

The utility of platelet catecholamine determination in assessing sympathetic nervous system activity depends on the extent to which transient fluctuations of plasma catecholamine concentration can affect platelet catecholamine content. In order to quantitate the relationship between plasma and platelet catecholamine content, the concentrations of norepinephrine, epinephrine and dopamine needed to produce an increase in platelet catecholamines in vitro were determined. The threshold for epinephrine accumulation was 10(-9)M while the thresholds for norepinephrine and dopamine were an order of magnitude higher. The uptake of catecholamines was also found to differ with regard to the time course and the amount of catecholamine accumulated. For example, after 2 h in the presence of equimolar (2 × 10(-8)M) concentrations of catecholamine the platelet content of norepinephrine doubled and epinephrine rose 10-fold and dopamine 20-fold. When platelets that had been loaded with catecholamines were suspended in catecholamine-free buffer, significant amounts of catecholamines were still retained in the platelets after 3 h, but retention of norepinephrine was greater than that of epinephrine. These results indicate the importance of the concentration of the particular catecholamine, duration of exposure of platelets to the catecholamine and the ability of platelets to retain catecholamines, in determining the relationship between plasma and platelet catecholamine content.

Pharmacotherapy of human hypertension is effective, safe and well-tolerated. Antihypertensive drugs are of three broad classes: diuretics, sympatholytics and vasodilators. The use of each class is discussed and a summary of therapeutic considerations offered for representative agents. Recent trends in antihypertensive therapy are identified.

Nine healthy humans received sequential 80-min infusions of saline and epinephrine (EPI) at 0.55 and 2.75 micrograms X min-1 X m-2 to determine whether increases in arterialized venous plasma EPI within the physiological range affect platelet EPI levels. The platelet EPI concentration was significantly higher than basal levels only during the 2.75 micrograms X min-1 X m-2 EPI infusion (P less than 0.02). To assess the role of platelets in EPI clearance from plasma, four human subjects underwent a 2.75 micrograms X min-1 X m-2 EPI infusion during beta-adrenergic blockade with propranolol. Propranolol decreased plasma EPI clearance (P less than 0.01) and increased both the plasma and platelet EPI concentrations (P less than 0.01) during the EPI infusion. To determine the changes in plasma and platelet EPI during and after EPI infusion, seven subjects received an 80-min EPI infusion at 2.75 micrograms X min-1 X m-2. After discontinuation of the EPI infusion, plasma EPI levels returned to base line within 30 min, whereas platelet EPI levels were significantly elevated above base line for 120 min (P less than 0.02 vs. base line). Platelets concentrate EPI during increases in plasma EPI, which are similar to the plasma levels seen in physiological and pathophysiological states in humans. The accumulation of catecholamines by platelets may be an additional mechanism in the regulation of plasma catecholamine levels in humans.

Plasma catecholamine and renin activity levels were measured across a range of dietary sodium intakes (10--300 mEq/day) in 20 normal male volunteers. Supine plasma norepinephrine levels presented a triphasic pattern in relation to urine sodium, whereas epinephrine levels were not significantly altered by sodium intake, and renin showed the well-known hyperbolic relationship to urine sodium excretion. Highest supine norepinephrine values occurred at low salt intakes, the lowest when sodium excretion was between 100 and 180 mEq/day, and intermediate when sodium excretion was greater than 180 mEq/day. These findings show that sodium intake is an important consideration in the interpretation of plasma norepinephrine levels.

Digital volume pulse maximum dilation was determined in 27 patients with borderline essential hypertension (BHT) and 28 age-matched normotensive controls (NT). Finger pulse volume (PV) and finger systolic pressure (SBP) were measured by pneumoplethysmography during vasodilation induced by combining direct and reflex heat dilation and reactive hyperemia. Finger SBP was higher (p less than 0.01) in BHT than in NT (120 +/- 18.7 vs. 104 +/- 14.8 mm Hg, respectively); PV was lower (p less than 0.01) in BHT than in NT (9.7 +/- 4.2 vs. 15.3 +/- 6 ml/5 ml finger X 10(-3). Pulse volume correlated inversely with SBP in BHT (r = -0.40, p less than 0.05) but was unrelated to SBP in NT. Pulse volume was not altered by high or low sodium intake in BHT or NT despite significant changes in plasma renin activity (PRA). In BHT finger vessels are less distensible at a higher pressure than in NT. This abnormality is demonstrable during maneuvers to withdraw sympathetic tone and is not influenced by alteration of PRA. These data support the concept that BHT can produce structural vascular change, and demonstrate that this abnormality can be detected by a relatively simple method.

Personal, social, and medical factors unique to individual patients have a bearing on the efficacy of specific antihypertensive agents and on the frequency and severity of side effects. The factors relate to age, sex, occupation, potential for adherence to a prescribed program of therapy, and associated health problems. The importance of a simple, inexpensive program is emphasized.

A patient education booklet was developed, based on patient behaviours identified as necessary for the control of hypertension. Use of the booklet increased patients' knowledge and helped to establish the desired behaviours. There were no adverse psychological effects on the subjects. Long-term usefulness of the booklet was assessed in 148 patients, whose motivation increased without increased anxiety. We conclude that educationally sound instructional materials complement the medical management of hypertension.

Platelet catecholamine content was determined by radioenzymatic assay in 16 patients with elevated plasma norepinephrine or epinephrine or both and a clinical picture suggesting pheochromocytoma. Twenty-two normal subjects served as controls. Pheochromocytoma was documented in 10 patients, all of whom had markedly elevated platelet catecholamines. The other six patients had no tumor, and their platelet catecholamine levels were normal. Platelet catecholamines tended to return to normal more slowly than plasma catecholamines after removal of the pheochromocytoma, suggesting that platelets were rich in stored catecholamines. Determination of platelet catecholamine content is a helpful aid to the diagnosis of pheochromocytoma in patients with suggestive but not diagnostic elevations of the plasma catecholamine concentration.

This study tested the hypothesis that the Type A behavior pattern and its components are associated with increased activity of the sympathetic nervous system. To do this, we employed two new markers of sympathetic tone--pupil size and platelet catecholamine content. Thirty-three healthy males were blindly rated for Type A behavior and verbal stylistic components by Structured Interview. Adrenergic tone to the pupils was assessed from pupil diameter recorded by infrared television pupillometry, and pupil alpha-adrenergic sensitivity was estimated from mydriatic response to ophthalmic phenylephrine. Platelet epinephrine and norepinephrine contents were assayed because these levels are associated with chronic, long-term circulating catecholamine levels. The results showed Type As had consistently larger pupil diameters than Type Bs (p = 0.03, 0.03, and 0.01). There was no difference in pupillary response to phenylephrine instillation between groups. Platelet epinephrine content was greater in Type A subjects (chi 2 = 4.25, p less than 0.04, t = 1.6, p = 0.06). Only the component of explosiveness was modestly associated with resting pupil size, and no components significantly predicted platelet catecholamines. We conclude that the results of these two new markers of autonomic activity, namely, pupil size and platelet epinephrine, suggest that Type A behavior is characterized by increased sympathetic nervous system tone although we cannot rule out the possibility of decreased activity of the parasympathetic nervous system.

The major findings of a review of the literature on platelet aggregation in hypertensive human subjects and the effects of antihypertensive agents were as follows: (1) There is an increased platelet aggregatory response to epinephrine and ADP in hypertensives with MAP greater than 120 mmHg. (2) Treatment with propranolol decreases the aggregatory response to ADP, but it may enhance the response to epinephrine. (3) Treatment with calcium blockers in normotensives decreases the aggregatory response to epinephrine. Further work needs to be done to answer the questions raised by this review. Since the major goal, yet unachieved, of antihypertensive therapy is reduction of the incidence of CHD, the anti-thrombotic or thrombotic potential of antihypertensive agents must be known. Future clinical trials of drug therapy for hypertension should be designed to include at least a determination of platelet aggregation in response to both ADP and epinephrine.

We were able to observe the effect of withdrawal of endogenous sympathetic drive in a hypertensive patient with an aldosterone-secreting adrenal adenoma. Acute stimulation of both carotid sinus nerves lowered blood pressure to normotensive or hypotensive levels by reducing peripheral resistance. When chronic carotid sinus nerve stimulation was discontinued, peripheral resistance and blood pressure increased. These data suggest that the sympathetic nervous system is important in the maintenance of hypertension in established primary aldosteronism.

In order to assess the relationship of occlusive digital artery disease to the presence or subsequent appearance of systemic illness in patients with Raynaud's phenomenon, the records of 147 patients with Raynaud's phenomenon, subdivided on the basis of quantitative finger plethysmographic results into those with and without occlusive digital artery disease, were reviewed. Patients with definite scleroderma were excluded from the study. Occlusive digital artery disease was detected in 62 percent of the 147 cases. A cause for Raynaud's phenomenon was found at initial evaluation in 34 percent of patients with occlusive digital artery disease and 24.9 percent of patients without it. Follow-up status was ascertained in 56 patients with no cause for Raynaud's phenomenon discovered at initial evaluation. During a follow-up period averaging five and a half years, systemic illness became apparent in 43.8 percent of those with occlusive digital artery disease and only 16.7 percent of those without it. Connective tissue diseases, primarily scleroderma, dominated in both categories, but carcinoma was also a problem and appeared only in patients with occlusive digital artery disease. The presence of occlusive digital artery disease in patients with Raynaud's phenomenon of no apparent cause warrants greater concern and closer follow-up for the development of cancer or connective tissue disease. Digital plethysmography for the detection of occlusive digital artery disease is an important part of the evaluation of patients with Raynaud's phenomenon.

Increments in heart rate during the TNG test (sublingual nitroglycerin with assumption of upright posture), passive head-up tilt, and postrecumbency standing were compared to the effects of intravenous isoproterenol in 15 mild hypertensives during administration of placebo and two dosage levels of propranolol. TNG test results correlated with responsiveness to isoproterenol, but nitroglycerin tachycardia was reduced only about 50% during propranolol treatment. The TNG response was almost maximally inhibited by 160 mg/day of propranolol while the response to postrecumbency standing was inhibited only by a dose of 320 mg/day. The results indicate that: (1) the TNG test is of limited value in the assessment of beta adrenergic blockade in hypertensive patients, and (2) propranolol in a dose of 160 mg/day induces near-maximal cardiac blockade.

The effect on blood pressure of high (400 mg/day-S400) and moderate dose (200 mg/day-S200) spironolactone and chlorthalidone (100 mg/day-C100), given in a random double-blind manner was related to plasma renin activity and plasma volume in 38 essential hypertensives. The fall in pressure from a control of 154/103 mm Hg was essentially the same after four weeks of each drug--S400 deltaBP 24/13 mm, S200 18/9 mm, C100 17/12 mm (all P less than 0-001). Twelve of 37 patients (32%) had low initial renin, but this appeared as responsive to the chlorthalidone stimulus as that of the normal renin group. The antihypertensive effect of all regimens was unrelated to plasma renin activity. Plasma volume was significantly lowered at the end of each treatment period, but the decline could not be correlated with blood pressure effects. Patients with initially low plasma volume were more likely to respond to S400 (r = 0-545, P less than 0-001), whereas the antihypertensive effect of the S200 and C100 regimens was independent of this variable.

1. The relationship between baroreflex sensitivity (BRS) and arterial compliance index (ACI) has been investigated (a) in paired subjects matched in one instance for systolic blood pressure with differing ages, and (b) in another instance matched for age with differing systolic blood pressures. 2. There was a significant negative correlation between BRS and age and between ACI and age in the twelve systolic blood pressure-matched subjects. 3. A significant negative correlation of systolic blood pressure with both BRS and ACI was observed in the fourteen age-matched subjects. 4. Both BRS and ACI appear to decrease with increasing age and systolic blood pressure. This decrease in BRS is probably due at least in part to the observed reduction in arterial distensibility.

The antihypertensive effect of captopril was assessed during short- and long-term periods in ten patients with elevated blood pressure readings that were uncontrollable by standard therapy (supine diastolic blood pressure of greater than 100 mm Hg with a regimen of propranolol hydrochloride, hydralazine hydrochloride, and hydrochlorothiazide). When given alone, captopril therapy was unable to normalize the blood pressure in any patient. The addition of hydrochlorothiazide to the captopril therapy normalized the blood pressure in one patient and sharply improved the blood pressure in four others. The blood pressure in the remaining patients responded inadequately to this combination. The addition of propranolol to captopril and hydrochlorothiazide reduced the blood pressure further in most cases (seven on the ten patients had normal blood pressure readings while they received these three drugs). In four patients, the blood pressure response to the added propranolol was unrelated to changes in plasma angiotensin II concentration. Captopril was helpful in the management of refractory hypertension in most cases.

Animal experiments indicate that angiotensin II can, under some circumstances stimulate the sympathetic nervous system at a number of different sites. In order to determine whether such a relationship of the renin-angiotensin and sympathetic nervous system exists in man, we increased (by intravenous infusion), or decreased (by administering the oral converting enzyme inhibitor captopril) circulating angiotensin II levels and monitored plasma adrenaline and noradrenaline responses. Angiotensin II infusions did not increase plasma catechol-amines, and lowering of angiotensin II by captopril treatment in patients with severe hypertension or congestive heart failure failed to alter plasma adrenaline or nor-adrenaline levels. Whether physiological levels of angiotensin II are capable of interacting directly with the sympathetic nervous system in man remains to be demonstrated.