Angiotensin converting enzyme inhibition and vascular hypertrophy in hypertension

Summary The pathogenesis of hypertension is associated with a remodeling of vascular structure. Folkow has postulated that the decreased luminal area and thickened medial layer in hypertensive vessels enhances the vasoconstrictive response to vasoactive agents. It is hypothesized that this increase in vascular reactivity may serve to perpetuate hypertension. A growing body of evidence suggests that autocrineparacrine vasoactive substances and growth factors modulate vascular structure in hypertension. We speculate that therapeutic interventions that normalize blood pressure as well as reverse the vascular remodeling process may have special clinical value. The role of the paracrine renin-angiotensin system and angiotensin converting enzyme inhibitors in hypertension is discussed in this context.     

Angiotensin converting enzyme inhibitors

This review focuses on the use of angiotensin converting enzyme (ACE) inhibitors in hypertensive diseases. Specifically discussed are: proposed mechanisms of action, the pharmacology of the commercially available ACE inhibitors (captopril, enalapril, and lisinopril), their renal effects, and their safety and efficacy. The ACE inhibitors are assuming a dominant role in our therapeutic armamentarium, in that they are well-tolerated and very effective in the treatment of mild, moderate or severe hypertension.     

Angiotensin converting enzyme inhibitor cough: Lessons from heart–lung transplantation

Coughing is a frequent side-effect of angiotensin converting enzyme (ACE) inhibitors. Its pathogenesis is thought to be related to the local accumulation of tachykinins although the role of extrinsic cholinergic pathways is unclear. The development of an ACE inhibitor induced cough in two patients who have undergone heart–lung transplantation and in whom cholinergic pathways remain denervated supports the hypothesis of a 'local' mechanism.     

Angiotensin converting enzyme inhibitors in arterial hypertension

We review the different cardiovascular effects exerted by angiotensin converting enzyme inhibitors, obtained in several experimental and clinical studies in the last twenty years, in patients with arterial hypertension and different cardiovascular pathologies related to the hypertensive process. We will review the mechanistic basis of the cardiovascular protective effects of angiotensin converting enzyme inhibition. These drugs, as monotherapy or combined therapy, can achieve blood pressure control in a high proportion of hypertensive patients; in hypertensive patients with diabetes these drugs are especially indicated, and also are the drugs of choice in diabetic hypertensive patients with cardiac dysfunction due to ischaemic cardiomyopathy. This group of drugs has the highest effect among the drugs available today in reducing left ventricular hypertrophy associated with the hypertensive process. There are many experimental and clinical data that suggest the potential role of the angiotensin converting enzyme antagonists limiting the atherosclerotic process.     

Angiotensin converting enzyme inhibitors in renal diseases

Chronic diffuse renal diseases, involvement of the kidney in systemic and metabolic disorders are characterized by steady progression of renal pathology with loss of functional nephrons, lowering of renal functions and gradual development of chronic and eventually terminal renal failure. Basic mechanism of progression of chronic renal failure is activation of local renin-angiotensin system with intrarenal formation of a potent vasoconstrictor and growth factor - angiotensin II. Potentially nephroprotective effect can be achieved by pharmacological block of angiotensin II by angiotensin converting enzyme inhibitors. It has been shown in some prospective studies (AIPRI, REIN, ACEi-1 Trial, MICRO-HOPE) that the use of these drugs is associated with slowing of progression of renal pathology irrespective of its etiology and delayed development of terminal renal failure in patients with preexisting chronic renal insufficiency. Data available indicate that angiotensin converting enzyme inhibitors should be first line agents in the treatment of patients with chronic diffuse renal diseases of various etiology and diabetic nephropathy.     

Angiotensin converting enzyme in bronchoalveolar lavage in ARDS

Angiotensin converting enzyme (ACE) is present in the endothelial cells of the normal lung where it converts angiotensin I to angiotensin II and inactivates bradykinin. It has been suggested that during endothelial injury ACE is sloughed into the blood, and that if the alveolar capillary membrane is injured, also into the alveolar lining fluid. Seven patients with adult respiratory distress syndrome (ARDS), were compared to 11 normal control subjects, nine patients with sarcoidosis, and six with idiopathic pulmonary fibrosis. Total, differential cell counts and ACE determinations were performed on bronchoalveolar lavage fluid in the ARDS group. ACE was detectable in the BAL of all but one ARDS patient. It was concluded that BAL ACE is elevated in some ARDS patients, especially those with infectious causes of lung injury. Increased ACE may reflect endothelial damage or local increase in ACE production in response to sepsis.