Conventional Antihypertensive Drugs Research Articles

Non-peptide angiotensin type 1 receptor antagonists in the treatment of hypertension.

Angiotensin II (Ang II) acts at the cellular level on two receptor subtypes: the AT1 receptor which can be blocked by losartan and its analogues (the 'sartan family'), and the AT2 receptor that does not react with the above antagonists but which can be blocked by different compounds, such as PD123319. AT1 receptor blockade has proven to be a highly effective means of interference with the renin-angiotensin system (RAS) and hence of reducing high blood pressure. As a result of the terminal blockade of the RAS cascade, circulating Ang II levels tend to rise two- to threefold. The free access of such enhanced levels to uninhibited AT2 receptors may be clinically relevant, as argued in the present review. The most extensive experimental and clinical experience with AT1 receptor blockade so far has been obtained with the pioneer drug losartan, although major contributions have also been made on candesartan cilexetil, irbesartan and valsartan. All of these four drugs have been instrumental in substantial clinical trials, serving as sources of information in the clinically oriented part of this review. AT1 receptor blocking drugs generally provide a relatively gradual decrease in blood pressure, which is comparable to that obtained with conventional anti-hypertensive drugs. Clinical trials reveal an astounding lack of drug-related adverse effects, scoring even better than placebo in terms of frequencies and sometimes patterns. The trough/peak ratio on single dosages seems to have been mastered, particularly with the second generation of AT1 receptor blockers, as is evident from 24 h ambulatory blood pressure monitoring. Combination with low-dose thiazide regimens is well established. Intermediate endpoints (micro-albuminuria and left ventricular hypertrophy) appear to be controllable. Morbid cardiovascular sequelae are currently under study in comparison with beta- and calcium channel blockade.

Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria

Stratum 2 of the Ramipril Efficacy in Nephropathy (REIN) study has already shown that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, angiotensin-converting enzyme (ACE) inhibition reduced the rate of decline in glomerular filtration and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF) found in controls on placebo plus conventional antihypertensives. In REIN stratum 1, reported here, 24 h proteinuria was 1 g or more but less than 3 g per 24 h. In stratum 1 of this double-blind trial 186 patients were randomised to a ramipril or a control (placebo plus conventional antihypertensive therapy) group targeted at achieving a diastolic blood pressure of less than 90 mm Hg. The primary endpoints were change in glomerular filtration rate (GFR) and time to ESRF or overt proteinuria (> or =53 g/24 h). Median follow-up was 31 months. The decline in GFR per month was not significantly different (ramipril 0.26 [SE 0.05] mL per min per 1.73m2, control 0.29 [0.06]). Progression to ESRF was significantly less common in the ramipril group (9/99 vs 18/87) for a relative risk (RR) of 2.72 (95% CI 1.22-6.08); so was progression to overt proteinuria (15/99 vs 27/87, RR 2.40 [1.27-4.52]). Patients with a baseline GFR of 45 mL/min/1.73 m2 or less and proteinuria of 1.5 g/24 h or more had more rapid progression and gained the most from ramipril treatment. Proteinuria decreased by 13% in the ramipril group and increased by 15% in the controls. Cardiovascular events were similar. As expected, the rate of decline in GFR and the frequency of ESRF were much lower in stratum 1 than they had been in stratum 2. In non-diabetic nephropathies, ACE inhibition confers renoprotection even to patients with non-nephrotic proteinuria.

Captopril comparable to conventional antihypertensives?

Captopril comparable to conventional antihypertensives?

Progress Report on the Nordic Diltiazem Study (NORDIL): An Outcome Study in Hypertensive Patients

NORDIL--the Nordic Diltiazem Study (NORDIL)--is a prospective, randomized, open blinded-endpoint (PROBE), multicenter, parallel-group morbidity/mortality outcome study in hypertensive patients designed to compare an intervention strategy based on the calcium antagonist diltiazem with a strategy based on conventional antihypertensive drug treatment (diuretics or beta-adrenergic blockers). Patient recruitment was started in Norway and Sweden in September 1992, and ended on December 15, 1996, when 10.896 male and female patients, aged 50-74 years, with essential hypertension had been randomized. In this paper we describe the baseline data of the patient cohort and blood pressures achieved in the two treatment groups during the early part of the study. The patient cohort consists of 5294 males and 5602 females with a mean age of 59.6 and 60.3 years, respectively. Concomitant disorders and risk factors in the cohort are: smoking 22%, ischemic heart disease 3.0%, previous myocardial infarction (MI) 2.0%, previous stroke 1.5%, diabetes mellitus 7.0%, and renal impairment 0.3%. There were no differences between the treatment groups in these respects. The blood pressure treatment goal is a target diastolic blood pressure of < or =90 mmHg or a 10% diastolic blood pressure reduction from the inclusion pressure. In the treatment group randomized to a diltiazem-based treatment strategy, blood pressure was 174/106 mmHg at baseline and 156/90 mmHg after 12 months of follow-up on active treatment. In the group randomized to a conventional treatment strategy, baseline blood pressure at randomization was 173/106 mmHg and 153/90 mmHg after 12 months on active therapy. The NORDIL study will terminate on October 31, 1999 and the final results should be available by mid-2000.

Effects of antihypertensive therapy on progression of diabetic nephropathy

There is a clear relationship between hypertension and the microvascular complications of diabetes. Genetic predisposition to hypertension has been correlated to the risk of diabetic nephropathy in type I diabetes, and hypertension is a well known risk factor for developing nephropathy in patients with type II diabetes. Multiple studies have emphasized the importance of hypertension on renal disease progression, and blood pressure control with conventional antihypertensive drugs slows the rate of renal function loss in diabetic nephropathy. Furthermore, evidence of the role of renin-angiotensin system (RAS) on progression of renal damage has focused much interest on the therapeutic action of the RAS blockade. In patients with type I diabetes, blocking the RAS with angiotensin converting enzyme (ACE) inhibitors prevents progression from microalbuminuria to overt nephropathy, and in overt nephropathy decreases the gradual loss of renal function beyond its blood pressure lowering effect. Less clinical information is available in type II diabetic nephropathy, but our experience and some recent studies suggest that ACE inhibitors also have a renoprotective action in type II diabetes. The role of calcium channel blockers in diabetic nephropathy is not clear. Several short-term studies with the first generation dihydropyridine calcium antagonists showed a lower effect on urinary albumin excretion and a more rapid progression to renal failure than with ACE inhibitors. However, other calcium channel blockers, particularly of the non-dihydropyridine type, have been shown to have a beneficial effect on diabetic nephropathy, decreasing proteinuria and slowing progression.

Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial

The Ramipril Efficacy In Nephropathy (REIN) study found that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, ramipril safely reduced the rate of decline of the glomerular filtration rate (GFR) and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF), as compared with placebo plus conventional antihypertensive drugs at the same level of blood pressure control. At the end of the core study patients continued on or shifted to ramipril and were formally enrolled into the REIN follow-up study. 97 patients entered the follow-up study. Patients originally randomised to ramipril continued with the same daily dose (n=51), whereas those originally on placebo plus conventional antihypertensive drugs switched to ramipril after the first visit of the follow-up study (n=46). Ramipril (1.25 to 5.00 mg/day) and conventional antihypertensive therapy were targeted at achieving diastolic blood pressure under 90 mm Hg. The main efficacy variables were GFR decline and ESRF (need for dialysis). Analysis was by intention to treat. During the follow-up study the mean rate of GFR decline per month decreased from 0.44 (SD 0.54) mL/min per 1.73 m2 in the core study to 0.10 (0.50) mL/min per 1.73 m2 in patients originally randomised to ramipril (p=0.017), and from 0.81 (1.12) to 0.14 (0.87) mL/min per 1.73 m2 in those originally randomised to placebo plus conventional antihypertensive therapy (p=0.017). At the final visit, mean absolute GFR values were 12 mL/min per 1.73 m2 higher (33% better) in patients randomised to ramipril than in those assigned placebo (n=26 and 17, respectively: 35.5 [19.0] vs 23.8 [9.4] mL/min per 1.73 m2, p=0.01). 19 of the patients originally on ramipril versus 35 switched from placebo to ramipril progressed to ESRF (p=0.027) during the whole observation period; of these, six (8%) versus 14 (16%) reached that endpoint during the follow-up study; and the risk ratios were 1.86 (95% CI 1.07-3.26) over the whole observation period and 2.95 (1.13-7.68) during follow-up. Beyond follow-up at month 36, the incidence of ESRF was zero in patients originally randomised to ramipril but 30% in patients on placebo plus conventional antihypertensive therapy. In patients with chronic nephropathy and high risk of rapid progression to ESRF, ramipril reversed the tendency of GFR to decline with time. Moreover, a treatment period of sufficient duration (> or =36 months) eliminated the need for dialysis. Even patients previously treated with antihypertensive drugs other than angiotensin-converting-enzyme inhibitors benefited from shifting to ramipril.

The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C Li) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C Li, was 1 to 54 mL/min. Calculated fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% ( P < 0.001) and C Li was 88% ( P < 0.01) of the baseline values, APR and FPR had not changed significantly, and potassium clearance was significantly decreased. Through the rest of the study period, APR remained nearly unchanged and FPR even increased in the enalapril group. In the group of patients randomized to treatment with conventional antihypertensive drugs (n = 35), C Li was unchanged until severe reduction in GFR, APR and FPR decreased gradually, and potassium clearance was almost unchanged. These differences in tubular function between the two treatment regimens were significant ( P < 0.05). An unchanged or increased APR in either treatment regimen was associated with a long-term slower progression of renal failure. Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group ( P < 0.01), whereas the clearances of immunoglobulin G and retinol-binding protein were unchanged in this group. In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional antihypertensive therapy. During ACE inhibition, the reabsorptive capacity of the proximal tubule appeared to be better preserved, which might be of importance for the beneficial effect of this treatment in chronic renal disease.

Inhibitory effects of antihypertensive drugs on mesangial cell proliferation after anti-thymocyte serum (ATS) — induced mesangiolysis in spontaneously hypertensive rats

The effects of antihypertensive drugs on mesangial cell proliferation were studied in spontaneously hypertensive rats (SHR) with anti-thymocyte serum (ATS) - induced glomerulonephritis. Rats were treated with either enalapril (Group 1), nifedipine (Group 2), or reserpine + hydrochlorothiazide + hydralazine (Group 3), or were untreated (Group 4). The animals were sacrificed 2, 4 and 7 days after ATS injection and the glomerular cell number and degree of mesangial area expansion were examined. A marked, similar decrease in glomerular nuclear cell number (NC) due to severe mesangiolysis was observed in all of the groups on day 2. Thereafter, an increase in NC reflecting mesangial cell proliferation after mesangiolysis occurred in Group 4 on days 4 and 7. In Groups 1 and 2, the NC was significantly smaller than that in Group 4 on days 4 and 7, indicating suppression of mesangial cell proliferation. In Group 3, however, the number of NCs did not differ from that in Group 4 on days 4 and 7, indicating a lack of such suppression by conventional antihypertensive drugs. The degree of mesangial area expansion (MS) showed the same pattern as mesangial cell proliferation. That is, the rapid increases in MS seen in Group 4 on days 4 and 7 were apparently suppressed in Groups 1 and 2, but not in Group 3. Our in vivo observations that both an angiotensin converting enzyme (ACE) inhibitor and a calcium channel blocker suppress mesangial cell proliferation and mesangial area expansion suggest that these agents have practical implications in the treatment of mesangial proliferative glomerular diseases through the suppression of excess mesangial cell proliferation.

Response of hypertension to conventional antihypertensive treatment and/or steroidogenesis inhibitors in Cushing's syndrome

To evaluate the effect of conventional antihypertensive drugs and/or inhibitors of steroid production in the management of hypertension in Cushing's syndrome. A retrospective open clinical study with pre- and post-treatment assessment. A university hospital, where patients were initially admitted and then followed-up in an ambulatory clinic over a period of 6 years. Forty consecutive hypertensive patients with Cushing's syndrome. Patients were divided into two groups according to the different management of hypertension. The first group (group 1) of 28 patients included those treated with antihypertensive drugs at full dose (diuretics, calcium antagonists, angiotensin converting enzyme [ACE] inhibitors, as single agents or in combination). The second group (group 2) of 12 patients received ketoconazole alone. Blood pressure variations compared to pre-treatment levels. Blood pressure normalization was obtained in four of the 28 patients of group 1. In 12 of the remaining patients, ketoconazole, an inhibitor of steroid production, was subsequently added and this normalized blood pressure in all but the one in whom cortisol was not decreased. In the 12 patients of group 2, ketoconazole alone lowered blood pressure within normal limits in all but one who had long-standing hypertension. In hypertensive patients with Cushing's syndrome, conventional antihypertensive therapy is mostly ineffective. Blood pressure response is satisfactory only after the restoration of normal cortisol levels, indicating the need for a specific treatment for hypertension in this disorder.

The place of alpha blockers in the treatment of hypertension.

Alpha 1 adrenoceptor antagonists are safe, effective, well tolerated drugs which can be used alone or in combination with other drug groups in a wide range of hypertensive patients. Alpha 1 blockers not only lower blood pressure but may improve insulin sensitivity and the adverse lipid profile in many hypertensive patients. In addition to causing few side effects, alpha 1 blockers are not contra-indicated in patients with associated cardiovascular or respiratory disease. Alpha 1 blockers offer the potential to improve the risk factor profile more than conventional antihypertensive drugs.

The Nordic Diltiazem Study (NORDIL). A prospective intervention trial of calcium antagonist therapy in hypertension.

NORDIL--the Nordic diltiazem intervention study was started in September 1992. This trial is a prospective randomized open blinded-endpoint (PROBE) multicenter, parallel-group study conducted in Norway and Sweden. The study is designed to evaluate the potential preventive effects of diltiazem compared with conventional antihypertensive drug treatment. Primary endpoints are cardiovascular mortality defined as fatal acute myocardial infarction, fatal acute cerebrovascular disease (stroke), sudden death and other fatal cardiovascular disease as well as cardiovascular morbidity defined as myocardial infarction and cerebrovascular disease (stroke). Secondary endpoints are total mortality, the development or deterioration of ischaemic heart disease, congestive heart failure, atrial fibrillation, transient ischaemic attacks, diabetes mellitus and renal insufficiency. Male and female patients, aged 50-69, with primary hypertension are randomly allocated to therapy starting with either diltiazem (180-360 mg daily) or conventional treatment (diuretics or beta-adrenergic blockers). Add-on therapy in the conventional treatment group excludes all types of calcium antagonists. The goal of treatment will be a target diastolic blood pressure of < or = 90 mmHg or a 10% diastolic blood pressure reduction. The NORDIL study will allow the detection of a 20% difference in cardiovascular mortality between the two groups with a power of 80% at the 5% significance level (two-sided test). A total of 12,000 patients will be recruited from about 480 primary Health Care Centers or hospital based Hypertension Units. Patients will be treated for an average period of 5 years.

Renoprotective action of angiotensin-converting enzyme inhibition in diabetes mellitus.

Roughly 40% of all diabetics, whether insulin dependent or not, develop persistent albuminuria, a decline in their glomerular filtration rate, and elevated blood pressure, i.e., diabetic nephropathy. Diabetic nephropathy is the single most important cause of end-stage renal disease in the Western world, accounting for over one-quarter of all end-stage renal disease. Systemic/glomerular hypertension plays a role in the initiation and progression of diabetic glomerulopathy. Angiotensin-converting enzyme (ACE) inhibitors are superior to conventional antihypertensive drugs in preventing the development of glomerular lesions in insulin-treated streptozotocin diabetic rats. Lowering of glomerular hypertension may be the crucial factor involved. Human studies suggest that ACE inhibitors postpone the progression to clinical overt diabetic nephropathy in normotensive diabetic patients with persistent microalbuminuria. ACE inhibitors combined with a diuretic reduce albuminuria and postpone renal insufficiency in hypertensive diabetics with overt nephropathy. No treatment modality other than antihypertensive treatment has yet been proven to be effective in protecting renal function in diabetic nephropathy. All previous reports dealing with the natural history of diabetic nephropathy have demonstrated a cumulative death rate between 50 and 77% 10 years after the onset of proteinuria. Effective antihypertensive treatment has reduced the cumulative death rate to 15-20% 10 years after the onset of nephropathy.

Reversible Renal Insufficiency due to Angiotensin Converting Enzyme Inhibitors in Hypertensive Nephrosclerosis

To review the incidence of reversible renal insufficiency in patients with hypertensive nephrosclerosis undergoing antihypertensive therapy. Retrospective analysis of 73 patients in a long-term blood pressure control study that compared the effects of an angiotensin converting enzyme (ACE) inhibitor plus conventional antihypertensive agents compared with placebo plus antihypertensive agents. Hospital-based outpatient treatment center. Patients were divided into group 1, which received enalapril plus conventional antihypertensives, and group 2, which received placebo plus conventional antihypertensives. Blood pressure and serum creatinine levels were measured, and imaging studies of the main renal arteries were done. In group 1, eight of 42 patients (19%, 95% CI, 9% to 34%) developed reversible renal insufficiency, defined as an unexpected increase in serum creatinine of 88 mumol/L or higher. Six episodes of reversible renal insufficiency occurred during July and August when temperatures were 32.2 degrees C to 37.8 degrees C (90 degrees F to 100 degrees F). Renal artery stenosis was excluded by renal arteriogram or ultrasonic duplex scanning. All eight group-1 patients had a significant decrease in mean arterial pressure below their baseline level during reversible renal insufficiency (mean change, -28 +/- 10 mm Hg, P less than 0.001). The increase in the serum creatinine level was inversely correlated with the decrease in the mean arterial pressure (r = -0.68, P less than 0.01). Reversible renal insufficiency was successfully managed by withdrawing or reducing enalapril as well as other antihypertensive agents. Subsequently, enalapril was tolerated by seven of the eight patients without recurrence of renal insufficiency. In contrast, none of 31 (CI, 0% to 11%) patients in group 2 developed reversible renal insufficiency despite the fact that both the incidence of decreases in mean arterial pressure in 6 of 31 patients (19%) and the magnitude of the decreases in mean arterial pressure (mean change, -33 +/- 16 mm Hg) were similar to those observed in group 1. Reversible renal insufficiency in hypertensive nephrosclerosis associated with ACE inhibitor therapy correlates with relative hypotension, is not dependent on renal artery stenosis, and can usually be managed by dose reduction.

Perindopril Safety and Tolerance in At-Risk Patients

The angiotensin-converting enzyme (ACE) inhibitors are effective in the treatment of hypertension and congestive heart failure. They improve the quality of life when compared with other conventional antihypertensive drugs. Perindopril, a new ACE inhibitor, is well tolerated and associated with fewer side effects than other types of antihypertensive agents. Moreover, it does not induce adverse metabolic changes such as hyperglycaemia and/or alterations in the blood lipid profile that could negate the benefits of lowering blood pressure. In hypertensive diabetic patients, perindopril decreases microalbuminuria without affecting the quality of glycaemic control and thereby may delay the progression of nephropathy. Therefore, perindopril appears to be an alternative first-line antihypertensive agent which may be useful in hypertensive diabetics.

Clinical Pharmacotherapeutics of Doxazosin

Doxazosin is the latest in a series of highly selective postsynaptic alpha 1-adrenoceptor inhibitors. It is readily absorbed, with high bioavailability and a relatively long plasma half-life, neither of which property is influenced by age. This accounts for the prolonged pharmacologic activity of doxazosin following a single oral dose. Its prime pharmacodynamic activity resides in its ability to counter sympathetic vasoconstriction of the systemic arteriolar resistance vessels and venous capacitance system, which enables the drug to target the major pathophysiologic abnormality in hypertension, i.e., the generalized systemic arteriolar constriction. The widespread vasodilation induced by doxazosin relieves both cardiac preload and afterload and, consequently, reduces left ventricular wall stress and myocardial oxygen consumption. In hypertension, doxazosin reduces blood pressure both at rest and during exercise by reduction of systemic vascular resistance without precipitating substantial reflex cardiac stimulation. The effects are maximal on the standing blood pressure between two and four hours after ingestion; due to doxazosin's relatively slow absorption, postural hypotension is infrequent. Its antihypertensive activity is maintained over 24 hours following a single oral dose, and the optimal dose range is 2 to 8 mg once daily. The antihypertensive efficacy of doxazosin has been shown to be comparable with that of other alpha-adrenoceptor inhibitors, beta-blocking drugs, diuretics, calcium antagonists, and angiotensin-converting enzyme inhibitors. In contrast to other conventional antihypertensive drugs, a unique feature of alpha-adrenoceptor-inhibiting drugs, including doxazosin, is their ability to reduce the plasma concentrations of triglycerides, total cholesterol, and low-density lipoprotein cholesterol and to increase high-density lipoprotein cholesterol concentration. This contrasts with the opposite effect on lipid levels induced by hydrochlorothiazide and atenolol seen in comparative studies. Side effects show no predilection for any organ system, and the overall incidence of such effects compares well with those of other commonly used antihypertensive drugs. This unique combination of antihypertensive efficacy and favorable effect on blood lipid levels indicates that once-daily treatment with doxazosin holds considerable promise in the treatment of hypertension, both from the point of view of its antihypertensive efficacy and also from its primary preventative potential.

DIET VERSUS DRUG TREATMENT FOR MILD HYPERTENSION IN OBESE MEN.

To compare the effectiveness of diet and conventional antihypertensive drug treatment, Berglund and colleagues randomized 61 middle-aged men with primary hypertension to either a weight-reducing, low-sodium diet or stepped-care drug therapy (with atenolol as the first choice) for one year. …

Metabolic Effects of Calcium Antagonists in Humans, with Emphasis on Carbohydrate, Lipid, Potassium, and Uric Acid Homeostases

Since metabolic side effects of conventional antihypertensive drugs could be one reason for the lack of improvement of cardiac morbidity and mortality, metabolic neutrality has become an important postulate of newer products such as the calcium antagonists (CA). Carbohydrate homeostasis--in spite of an anticipated deterioration derived from early in vitro experiments--has mostly been unaffected by CA therapy in humans, nondiabetic and diabetic. This was found in long-term studies in particular, whereas in acute or short-term trials with high dosages, minor alterations of insulin secretion and/or action were sometimes noted. These are negligible from a clinical point of view. Serum lipid profiles also were generally not disturbed by CA treatment, since most of the controlled long-term trials showed no change or even a potentially beneficial change. Minor lowering of plasma potassium levels during a CA regimen was exceptional and a rise of plasma uric acid values never reported; the latter may even decrease under certain circumstances. Thus, after reviewing more than 150 pertinent publications, we can state that the benefit of antihypertensive or antianginal treatment with a CA is in all likelihood not compromised by introducing known untoward metabolic cardiovascular risks.

Combined treatment of severe essential hypertension with the new angiotensin converting enzyme inhibitor ramipril

Ramipril is a newly synthesized angiotensin converting enzyme inhibitor without a sulfhydryl group in the molecule but with a prolonged duration of action. Efficacy, tolerance and safety of this drug were evaluated in 10 patients with severe essential hypertension. After a treatment period of at least 4 weeks with the conventional antihypertensive drug combination of a diuretic and a β-blocking agent with the vasodilator dihydralazine, their systolic and diastolic blood pressures averaged 161 ± 6 and 111 ± 2 mm Hg, respectively. Because diastolic blood pressure during this drug regimen was still > 105 mm Hg in all patients, the patients received ramipril initially at single daily doses of 5 mg in addition to their previous medication. The first dose of 5 mg ramipril resulted in a moderate but significant decrease in systolic and diastolic blood pressure in 9 of the 10 patients to 142 ± 5 and 104 ± 4 mm Hg (p < 0.01), respectively, between 3 and 6 hours after drug administration. In 1 patient blood pressure was unresponsive to ramipril and 1 patient complained of nausea and vomiting within the first week of treatment with ramipril. Within the following 8-week treatment period with a once-daily intake of 5 or, if necessary, 10 mg of ramipril, diastolic blood pressure normalized in the remaining 8 patients to <90 mm Hg. Systolic and diastolic blood pressure averaged 130 ± 5 and 83 ± 2 mm Hg, respectively, at the end of the 8-week treatment period with ramipril. Severe hypotension and reflex tachycardia were not observed. Other side effects such as cough, itching and circumscript erythema, which were observed in 3 patients, were mild and only transitory. No hematologic alterations or abnormalities in blood chemistry and renal function were noted during treatment with ramipril.

Prevalence of hypertension in white, black and Asian diabetics in a district hospital diabetic clinic.

In a District General Hospital Diabetic Clinic 40.0% of a random sample of diabetics under the age of 65 years of age were hypertensive. Black patients (48.9%) had greater (p less than 0.05) prevalence of hypertension than Whites (37.5%) and Asians (35.4%). Hypertension was more prevalent in females (49.1%) than males (33.0%) (p less than 0.001) in each ethnic group except Asians, and patients not receiving insulin had greater prevalence (45.6%) than those on insulin (30.7%) (p less than 0.001), except black diabetics where the reverse was found. There was a positive relationship between age and systolic (p less than 0.00001) and diastolic blood pressure (p less than 0.00001) and a negative association between duration of diabetes and diastolic blood pressure (p less than 0.004) on multiple regression analysis but no relationship was noted between blood pressure and either weight or blood glucose. Forty-six percent of all hypertensives were receiving conventional anti-hypertensive drug therapy; 38.7% were normotensive with similar results in each ethnic group and between the sexes. Isolated systolic hypertension was the commonest form of hypertension (48.3%) with isolated diastolic hypertension (4.9%) the rarest. These findings were observed regardless of the ethnic group or gender. Although in the majority of cases hypertension was mild these data confirm the importance of routine blood pressure measurement in diabetic patients.

Nadolol in hypertensive patients maintained on long-term hemodialysis

The pharmacokinetics, efficacy, and safety of nadolol were evaluated in hypertensive patients maintained on long-term hemodialysis. In nine patients the plasma elimination half-life of unchanged nadolol averaged 26 hours following a single 40 mg oral dose during the interdialytic period. Nineteen patients received nadolol once after each dialysis session. In addition, 12 of the 19 patients also received hydralazine and/or furosemide daily. Predialysis blood pressures and heart rates were significantly lower with nadolol than with combination or single therapy with conventional antihypertensive drugs, including other beta blockers. Nadolol administered only after each dialysis session (i.e., two or three times a week), in conjunction with hydralazine and/or furosemide, is an effective antihypertensive agent in hypertensive patients receiving long-term hemodialysis.