American Journal of Hypertension

Ritz, Eberhard; Fliser, Danilo; Siebels, Michael

doi: 10.1093/ajh/6.7.241Spmid: 8398007

The kidney may contribute to and be damaged by hypertension. Evidence from studies of renal transplant recipients and familial studies suggests a genetic component for the occurrence of hypertension and nephrosclerosis. Glomerular injury may result from glomerular hypertension caused by loss of autoregulation and afferent renal vasodilatation. Glomerular injury may be mediated by injury to endothelial cells, which, having lost their thromboresistance, may initiate intravascular coagulation and alter the balance between endothelin and endothelium-derived relaxing factor. Increased transit of proteinladen fluid into the mesangial space also may mediate hypertensive nephrosclerosis. Several studies have provided encouraging evidence that antihypertensive therapy, particularly with angiotensinconverting enzyme inhibitors or calcium antagonists, can slow the progression of renal damage. Am J Hypertens 1993:6:241S-244S

Applegate, William B.

doi: 10.1093/ajh/6.7.277Spmid: 8398012

In elderly patients, elevation of systolic blood pressure represents a more serious risk than elevation of diastolic blood pressure. Major trials of antihypertensive therapy in the elderly include the Systolic Hypertension in the Elderly Program, the Swedish Trial of Older Patients with Hypertension, the Medical Research Council Trial, and the Veterans Affairs Cooperative Study Group. Results of these trials indicate that, even for very elderly patients, reducing blood pressure reduces both morbidity and mortality from stroke and cardiac disease. Diuretics and calcium antagonists stand out as particularly efficacious in elderly hypertensive patients, β-Adrenergic blockers and angiotensin converting enzyme inhibitors may be less suitable in this patient population. Studies of the effects of antihypertensive therapy on the quality of life indicate that elderly patients can easily tolerate efficacious doses of antihypertensive drugs. Am J Hypertens 1993;6:277S-282S

Lüscher, Thomas F.; Tanner, Felix C.

doi: 10.1093/ajh/6.7.283Spmid: 8398013

The endothelium regulates vascular tone by releasing factors involved in relaxation and contraction, in coagulation and thrombus formation, and in growth inhibition and stimulation. Endothelium-dependent relaxations are elicited by transmitters, hormones, platelet substances, and the coagulation system, and by physical stimuli such as the shear stress from circulating blood. They are mediated by the endothelium-derived relaxing factor, recently identified as nitric oxide, which causes vasodilation and platelet deactivation. Other proposed endothelium- derived relaxing factors include a hyperpolarizing factor, lipooxygenase products, and the cytochrome P450 pathway. Endothelium-derived contracting factors are produced by the cyclooxygenase pathway and by endothelial cells, which produce the peptide endothelin-1, a potent vasoconstrictor that under normal conditions circulates at low levels. The endothelium produces both growth inhibitors— normally dominant—and growth stimuli. Denuded or dysfunctional endothelium leads to a proliferative response and intimal hyperplasia in the vessel wall; moreover, platelets adhere to the site and release potent growth factors. Endothelial dysfunction has numerous causes: Aging is associated with increased formation of contracting factor and decreased relaxing factor; denudation, such as by coronary angioplasty, impairs the capacities of regenerated endothelial cells; oxidized low-density lipoproteins and hypercholesterolemia interfere with nitric oxide production; hypertension morphologically and functionally alters the endothelium; and atherosclerosis markedly attenuates some endothelium- dependent relaxations. For patients with coronary bypass grafts, differences in endotheliumderived vasoactive factors between the internal mammary artery and the saphenous vein may be important determinants of graft function, with the mammary artery having more pronounced relaxations than the saphenous vein and thus a higher patency rate. Am J Hypertens 1993;6:283S-293S

Epstein, Murray

doi: 10.1093/ajh/6.7.251Spmid: 8398009

During the past decade, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they alter dramatically the response of this preparation to vasoconstrictor agents. Our recent studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, demonstrated that the preferential augmentation of glomerular filtration rate observed in the isolated perfused kidney is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics. Such disorders include radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the renal hemodynamic effects of calcium antagonists commend their use in the management of essential hypertension. Am J Hypertens 1993;6:251S-259S

Sowers, James R.; Standley, Paul R.; Ram, Jeffrey L.; Jacober, Scott; Simpson, Lori; Rose, Kelly

doi: 10.1093/ajh/6.7.260Spmid: 8398010

Subtle abnormalities of carbohydrate metabolism and overt diabetes mellitus are both associated with a substantial increase in the prevalence of hypertension and the accelerated development of atherosclerosis. Hypertension is also a presumed independent risk factor for atherosclerosis, although some of the atherogenic properties of hypertension may be related to the recently recognized subtle metabolic abnormalities commonly found in persons with essential hypertension. The results of epidemiologic studies suggest that the elevated fasting and postprandial insulin levels that often occur in patients with essential hypertension, as well as in patients with type II diabetes mellitus, are an independent risk factor for atherosclerotic cardiovascular disease. Elevated glucose levels in patients with diabetes and hypertension appear to contribute to the acceleration of atherosclerosis, perhaps through toxic effects on the vascular endothelium. Other cardiovascular risk factors that are accentuated in persons with carbohydrate intolerance and hypertension include abnormalities in platelet function, clotting factors, the fibrinolytic system, and dyslipidemia. The goals of both nonpharmacologic and pharmacologic therapy for patients with abnormal carbohydrate metabolism and hypertension are to decrease cardiovascular risk as well as lower blood pressure. Am J Hypertens 1993;6:260S-270S

Epstein, Murray

doi: 10.1093/ajh/6.7.239Spmid: N/A

Lund-Johansen, Per

doi: 10.1093/ajh/6.7.294Spmid: 8398014

Isradipine is a dihydropyridine calcium antagonist used for the treatment of hypertension. It is highly selective for vascular smooth muscle, more than cardiac muscle, and thus, lowers systemic blood pressure by reducing peripheral vascular resistance. Isradipine has less negative exotropic effect than other available calcium antagonists, and generally does not affect cardiac output, stroke volume, or heart rate when used chronically to treat hypertension. This agent has been shown to reduce left ventricular mass in patients with left ventricular hypertrophy after 5 to 10 months of therapy, without affecting cardiac output. Unlike most other calcium antagonists, isradipine can be used safely in hypertensive patients with congestive heart failure because its use in blood pressure lowering dosages does not compromise pump function. Isradipine has antiischemic properties and, in animals, antiatherosclerotic properties. Generally, it is a safe, well-tolerated agent for the treatment of hypertension with primarily benign effects on the heart. Am J Hypertens 1993;6:294S-299S

Hall, W. Dallas

doi: 10.1093/ajh/6.7.245Spmid: 8398008

Progressive renal failure is a significant complication of hypertension, a major cause of end-stage renal disease. In hypertensive patients, the markers of impaired renal function are abnormal levels of serum creatinine and microalbuminuria. Serum creatinine measurements, which can be adjusted for age and gender by using a simple formula, are used to estimate creatinine clearance and glomerular filtration rate. Microalbuminuria is an early sign of renal damage found in 20% to 30% of cases of essential hypertension and foretells the development of nephropathy and other complications. Current general guidelines for managing hypertension associated with renal impairment recommend controlling blood pressure, pharmacologically if necessary; adding a diuretic, if initial monotherapy is not effective; and reducing dietary sodium intake. Diuretic drugs remain the cornerstone of antihypertensive therapy for patients with renal failure, whereas β-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors have varying effects and continue to be investigated intensively. In a study undertaken by the National Institute of Diabetes and Digestive and Kidney Diseases, the different classes of antihypertensive drugs are currently being evaluated for their ability to slow progressive renal failure. Am J Hypertens 1993;6:245S-250S

Carr, Albert A.; Vrisant, L. Michael; Houghton, Jan L.

doi: 10.1093/ajh/6.7.271Spmid: 8398011

Among hypertensive patients, blacks are more likely than whites to have ischemia by electrocardiographic and 2 0 1Tl-myocardial stress imaging, possibly due to racial differences in the regulation of coronary blood flow or velocity. This investigation was undertaken to determine whether intensive antihypertensive therapy with two or more drugs can correct or reduce ischemia in black hypertensive patients. Thallium myocardial stress imaging and electrocardiographic and echocardiographic studies were performed on 13 black patients with essential hypertension and ischemic heart disease due to hypertensive heart disease (without significant obstructive epicardial coronary artery disease). The studies were made at baseline and after 4 to 48 months of intensive treatment, with a calcium antagonist and an angiotensin converting enzyme (ACE) inhibitor as the main components of the antihypertensive drug regimen. The majority of the patients with abolition or reversal of myocardial ischemia documented by 2 0 1Tl-myocardial imaging also had a significant reduction in left ventricular mass (LVM). However, some patients either did not have LV hypertrophy at baseline or had changes in LVM beyond the precision of the echocardiographic M-mode mass calculations. The finding indicated that factors other than reduction of LVM were involved in the reversal of the ischemia. The most likely factor was a change in the regulation of coronary blood flow. Reduction in LVM and reversal of myocardial ischemia determined either by electrocardiography or by thallium myocardial imaging studies may be considered indicators of the effectiveness of treatment. Am J Hypertens 1993;6:271S-276S