The relationship between diuretics and serum cholesterol in Hypertension Detection and Follow-up Program participants.

The effect of diuretics, mainly chlorthalidone, on serum cholesterol was studied in 7,006 of the Hypertension Detection and Follow-up Program (HDFP) hypertensive patients not on antihypertensive medication at baseline. Several investigators have reported that diuretic therapy increases serum cholesterol in treated subjects. However, data from two long-term studies indicated that no increase in cholesterol occurred after two years of diuretic treatment. In the present study, yearly changes in serum cholesterol in hypertensives treated with diuretics were observed. The results were in agreement with those reported from both short-term and long-term studies, in that a significant increase in cholesterol was observed in six months to one year into the study but not from the second to the fifth year of therapy. In fact, the serum cholesterol levels were the same as baseline values after two years of drug treatment and decreased slightly thereafter. In the untreated group, no change or a decrease in serum cholesterol was observed during the course of the study. The possible causes for changes in serum cholesterol concentration such as regression to the mean, change in body weight, baseline cholesterol concentration, and the action mechanism of diuretic drugs are discussed.

Cyclic nucleotide response to stimulation in isolated glomeruli from dog kidney.

The effects of biogenic amines on cyclic 3',5'-adenosine monophosphate (cAMP) and on cyclic 3',5'-guanosine monophosphate (cGMP) were studied in isolated glomeruli from dog kidneys. Of the agents tested, histamine produced the greatest increase in cyclic nucleotide activity. Isoproterenol, dopamine, epinephrine and norepinephrine also produced increases in cAMP and/or cGMP activity but of lesser magnitude. Propranolol decreased cyclic nucleotide levels. Glomeruli isolated from the outer cortex showed greater responses to stimulation than glomeruli from the inner cortex.

Variant ventricular tachycardia in desipramine toxicity.

We report a case of variant ventricular tachycardia induced by desipramine toxicity. Unusual features of the arrhythmia are repetitive group beating, progressive shortening of the R-R interval, progressive widening of the QRS complex with eventual failure of intraventricular conduction, and changes in direction of the QRS axis. Recognition of variant ventricular tachycardia is important because therapy differs from that of classic ventricular tachycardia.

Effects of antihypertensive therapy on cardiovascular response to exercise.

The effects of alpha methyldopa and hydrochlorothiazide therapy on exercise induced changes in arterial pressure, heart rate, rate-pressure product and total duration of exercise were evaluated with graded treadmill exercise. Although both agents were equally effective in reducing resting arterial pressure, alpha methyldopa appeared to provide slower build-up, a lower ceiling and more rapid recovery of arterial pressure in response to exercise stress than did hydrochlorothizide. Alpha methyldopa significantly reduced the degree of rise of the rate-pressure product (an index of myocardial oxygen consumption) during the exercise and recovery phases, whereas hydrochlorothiazide failed to do so. The total duration of exercise (an index of work capacity) was unchanged with either hydrochlorothiazide or alpha methyldopa. Therapy with alpha methyldopa presumably reduced myocardial oxygen demand without reducing work capacity.

Prostaglandins and hypertension.

Evidence is presented demonstrating the role of prostaglandins in salt metabolism and on peripheral vasodilation. A number of animal studies and observations in human hypertensive subjects suggest that the prostaglandin system plays a role in the pathogenesis of hypertension. The most striking and consistent finding over many decades of investigation is the relationship between dietary salt intake and the development of hypertension. Only a small percentage of any population develops hypertension. It is suggested that those people whose kidneys have an abnormal salt-handling capacity develop hypertension when challenged by a chronic high-salt intake. The salutary effects of diuretics or low-salt diet support this concept. Hypertension then is an expression of a renal abnormality. Prostaglandins, one of the renal salt regulating factors of the kidney, amy be involved in this abnormality. Whether there is a defect in the matabolic pathways or an unresponsiveness to normal stimuli of prostaglandins has not been determined. The use of prostaglandins in the treatment of hypertension is being explored. The demonstration that PGA1 can effectively lower blood pressure and reverse hypertensive emergencies indicates that prostaglandins probably have a broader, still unidentified role in the overall management of essential hypertension.

Effect of PGA1, PGE2, diazoxide on myocardial contractile force.

Experiments were conducted in anesthetized dogs comparing the effects of PGA1, PGE2, and diazoxide on myocardial contractile force (MC). The three agents were given in successive bolus injections intravenously in equidepressor doses and myocardial contractile force was measured by means of a strain-gauge arch sutured onto the right ventricle. The drugs were administered before and during ganglionic (hexamethonium) and beta-blockade (practolol). Both PGA1, and PGE2 caused a marked rise in MC, 24 and 20 per cent, respectively, before blockade and 10 and 11 per cent during blockade. Diazoxide caused only a minimal rise, 0.9 per cent, before blockade and a marked fall, 27 per cent, during blockade. Diazoxide administration during left ventricular bypass indicates that the decrease in MC is not a direct result of alterations in preload or after load. It is suggested that hypertensive patients treated with autonomic blocking agents may be more susceptible to heart failure in response to diazoxide therapy.

Autoregulation of renal blood flow in the puppy.

The ability of the immature kidney to autoregulate blood flow was investigated. Renal blood flow was measured by electromagnetic flowmeter. In six puppies, selective blockade of the intrarenal effects of angiotensin II (AII) by [1-sarcosine, 8-alanine]angiotensin II (anti-AII) administered into the renal artery did not change renal blood flow. During selective renal AII blockade, intravenous AII raised perfusion pressure from 76 +/- 2 to 100 +/- 6 mmHg. Renal blood flow increased from 1.59 +/- 0.29 to 1.98 +/- 0.59 ml/g kidney per min, but returned to control levels within 40 s in spite of persistent arterial pressure elevation. In another group of seven puppies, renal blood flow remained constant despite reduction of renal perfusion pressure by aortic constriction to 60 mmHg. In two of these seven puppies intrarenal anti-AII did not abolish autoregulation. Autoregulation of renal blood flow occurs in the puppy and is not influenced by inhibition of angiotensin. The renin-angiotensin system does not appear to be involved in the normal regulation of renal blood flow in the puppy.