Clinical presentation and management of patients with uncontrolled, severe hypertension: results from a public teaching hospital [abstract]

During the period 1st January, 2000 to 30th June, 2000, 156 patients who presented to the Accident and Emergency Department and had a blood pressure defined by WHO-ISH as grade 3 (severe) hypertension and received nifedipine 10 mg, were reviewed. The most common presentation was epigastric pain. All patients responded rapidly and effectively to nifedipine without tachycardia, gastrointestinal or other notable side effects of nifedipine. Contrary to current medical opinion, the study found that nifedipine was safe and effective, creating a possible dilemma for its use by primary care physicians in a developing country. (AU)

The characterization of the activity of a bark extract from Fagara martinicensis on the rat vas deferens

OBJECTIVE: An aqueous extract made from the bark of Fagara martinicensis (family Rutaceae) was examined for its effect on the isolated rat vas deferens. METHOD: The investigation involved measurement of isometric tension in the prostatic and epididymal portions of the isolated rat vas deferens which was anchored in an organ bath with physiological solution. Non-cumulative doses of Fagara martinicensis (FM) were added to the bath and the effects examined in the presence of receptor antagonists to characterize the actions of FM. Results before and after antagonist additions were compared. RESULTS: Non-cumulative addition of FM (1.6 mg/ml to 14.1 mg/ml) produced contractions of both portions of the vas deferens, with the epididymal portion showing greater sensitivity to the effects of FM. The contractions consisted of a rhythmic component superimposed on a phasic and tonic component. All components of the contractions were abolished by prazosin (2.1 uM), a selective a1-adrenoreceptor antagonist, and therefore it was concluded that FM contractions are due to agonist activities on these receptors. Since stimulation of a1-adrenoreceptora results in the mobilization of extracellular calcium into the muscle, the involvement of extracellular calcium was investigated with calcium channel antagonist, nifedipine (0.11-6.0 uM). Nifedipine inhibited all components of the contraction. This effect indicates that entry of extracellular calcium into the muscle was involved in all components of the contraction and further confirms a1-adrenoreceptor agonist action of Fagara martinicensis. CONCLUSIONS: Fagara martinicensis may therefore be a potential source of drugs with a1-adrenoreceptor agonist properties. (AU)

Hypertension and diabetic nephropathy: relationship, significance and management - abstract

During the past 10 years, several investigators have accumulated evidence for defining the relationship between systematic blood pressure levels and diabetic nephropathy. Studies showing the presence of insulin resistance in obese normotensive individuals, non-obese hypertensives, and in non-insulin-dependent diabetes mellitus (NIDDM) raise the possibility of shared pathogenic mechanisms in essential hypertension and diabetes mellitus. It is accepted that control of hypertension retards the progress of renal functional impairment in Diabetic Nephropathy (DN); what remains unknown is the class of antihypertensive agent best suited to this clinical situation. A case has been made for the angiotensin-converting enzyme inhibitors (ACE-Is) which have been demonstrated to have a renoprotective effect greater than can be attributed to lowering systemic blood pressure levels alone. Microalbuminuria is accepted as being an index of glomerular damage and a prognostic indicator for the development of DN and dip-stick detectable proteinuria. The ACE-I enalapril was shown to be more effective in reducing proteinuria than metoprolol, although both drugs reduced systemic blood pressure levels to a similar degree in the patients studied. On the other hand, the dihydropyridine calcium channel blocking agent (CCB), nifedipine, increased albuminuria whereas non-dihydropyridine CCBs did not. The animal experimental evidence suggesting glomerular hypertension as the mechanism through which albuminuria and subsequent glomerulosclerosis develop is persuasive. The differential renoprotective effects of the various hypertensive agents have therefore been related to their differing abilities to modulate both afferent and efferent glomerular arteriolar tone in a manner which produces net reduction in intraglomerular pressure. In clinical circumstances, selection of antihypertensive agents will be guided by the metabolic neutrality of the agent among other attributes, and ACE-Is and CCBs appear to have the most favourable profiles. Finally, the questions of how soon and how far to treat systemic hypertension in diabetics remain to be answered. Does one use ACE-iS to treat microalbuminuric and proteinuric patients who are still normotensive? To what level does one reduce the blood pressure in order to achieve optimal renoprotection in DN? There are now several survival studies of hypertensive patients which purport to show declining mortality with reduction of Diastolic Blood Pressure (DBP) levels to certain end-points, with a subsequent rise in mortality when DBP has been further reduced below approximately 85 mm Hg. The caveat of the "J-shaped" curve applies primarily to those patients with associated ischaemic heart disease, a condition which is frequently encountered in diabetes mellitus. Presumably, in those patients with associated left ventricular hypertrophy, reduction of DBP below a critical level compromises the coronary artery reserve and the blood supply to a mismatched ventricular mass. The ideal blood pressure lowering agent in DN is therefore one which reduces intraglomerular as well as systemic blood pressures, reduces albuminuria, is metabolically neutral, and reduces left ventricular mass. The ACE-Is and the CCBs fulfil these requirements but only ACE-Is decrease insulin resistance. Whether this latter "plus" will be shown to be critical is yet to be demonstrated (AU)