Michael Alderman

Cellular ions in hypertension, diabetes, and obesity : a nuclear magnetic resonance spectroscopic study

To investigate the cellular basis linking hypertension, non-insulin-dependent diabetes melllrus (NIDDM), and obesity, we used 31P and 19F nuclear magnetic resonance spectroscopy to measure intracellular pH (pHJ, free magnesium (M&), and cytosolic free calcium (Ca1) in erythrocytes of obese and NIDDM subjects with and without hypertension. Compared with nonnotensive, nondiabetic controls (Ca1 25.2 ±1.4 nM; Mg1232 ±8 μM), Cat was elevated in both nonnotensive (36.8±2.7 nM, sig=0.005) and hypertensive (43.4±2.9 nM, sig=0.001) NIDDM subjects, and Mg1 was concomitantly suppressed (nonnotensive: 206±ll μM, sig=0.05; hypertensive: 196±8 μM, sig=0.001). Similar but less striking changes were noted in obese subjects. Values of pH, were significantly lower (sig=0.05) in all hypertensive groups compared with their nonnotensive controls. Continuous relations were observed for all subjects between Ca1, and diastolic blood pressure (r=0.649,/7<0.001) and body mass index (r=0-565, p<0.001), between Mg, and diastolic blood pressure (r=-0.563, p<0.001) and fasting blood glucose (r=-0.580, p<0.001), and in diabetics, between pH1 and diastolic blood pressure (r= -0.680, p<0.001). Thus, the constellation of elevated Ca1, and suppressed Mg1 and pH1 levels is characteristic of the hypertensive state. These abnormalities of cellular ion handling in whole or in part common to hypertension, diabetes, and obesity may contribute to the pathophysiology of these syndromes and may help to explain their frequent clinical coexistence.

The determinants of hypertension awareness, treatment, and control in an insured population.

OBJECTIVESnThe purpose of the study was to identify the determinants of awareness, treatment, and control of hypertension in a population with full access to medical care.nnnMETHODSnUnionized New York City health care workers (n = 1394) with comprehensive medical insurance were screened for hypertension. Union records documenting all physician visits and prescription medications for the year before screening provided the opportunity to relate patterns of treatment to blood pressure outcomes.nnnRESULTSnOf the 409 employees found to have hypertension, 289 (71%) were aware of their condition and 201 (49%) had been treated, but only 51 (12%) had their blood pressure controlled at the recommended level (< 140/90 mm Hg). In a logistic regression model, the only variable of treatment associated with control was days of antihypertensive medication. The total number of physician visits was not associated with control.nnnCONCLUSIONSnThese findings demonstrate that in conventional community settings, even in the absence of financial barriers, treatment for hypertension continues to be characterized by poor outcomes. Improving access to primary care, without changes in the nature of that care, may not substantially improve blood pressure control.

Plasma prorenin: Cryoactivation and relationship to renin substrate in normal subjects

We previously demonstrated an inactive form of renin, termed prorenin, in the plasma of normal, hypertensive and anephric patients. Prorenin activity can be determined in plasma from the total renin activity after activation, minus the prior endogenous plasma renin activity. In the present study, conditions for cryoactivation of prorenin have been defined. Plasma prorenin is slowly converted to active renin-like material at -5 degrees C at pH 7.4. Activation takes four days and does not occur at pH 5.0. The degree of activation increases above pH 5 and is greatest between pH 7 and pH 9. Thus, almost no cryoactivation of prorenin occurs at the pH optimum for renin (5.7) in contrast to maximum activation at pH 7.4. No activation has been observed in the frozen state, but it does occur with decreasing rapidity at temperatures from -5 degress to +4 degress C. Since blood samples obtained for the determination of plasma renin activity are routinely chilled upon collection by most laboratories, some activatin of prorenin most likely occurs in all routine renin assays. The pH optimum of the enzymatic reaction of the activated prorenin in plasma is 5.8, the same as for renal renin, and the shape of the pH optimum curve is similar to that of renal renin added to human plasma. In a group of 23 normal subjects with plasma renin activity of 3.5 +/- 2.9 (SD), the activated prorenin increment was found to be significantly higher, 6.3 +/- 5.0 (SD) ng/ml/hour. Unlike plasma renin activity, prorenin activity in these normal subjects was directly related to the concentration of renin substrate (p less than 0.001). When the actual concentration of prorenin was calculated using renal renin as the reference standard, a direct relationship was also found between the concentration of prorenin and renin substrate (p less than 0.01). The observed relationship between prorenin and renin substrate concentrations might be a consequence of their regulation by common factors.

Diagnosis ex juvantibus. Individual response patterns to drugs reveal hypertension mechanisms and simplify treatment.

Heterogeneity of response to antihypertensive therapy is a well-recognized clinical phenomenon. An agent that is antihypertensive in one patient may increase blood pressure in another or have no effect in a third. We believe that this variety of individual response to drug treatment can provide a new framework for the study of hypertensive subjects. Different patterns of response elicited by sequential trials of individual drugs with different mechanisms of action (diuretics, calcium channel blockers, a-blockers, 0-blockers, and converting enzyme inhibitors) should provide another means to classify hypertensive patients into biologically relevant groups. The documentation and analysis of this therapeutic heterogeneity in relation to renm profiling and to other physiological and demographic parameters may add a new dimension to the investigation of the pathophysiology of hypertension; it may serve as a basis for more appropriate stratification of participants in cllnkal trials and may ultimately contribute to a more rational approach to patient management.

Absenteeism and labelling in hypertensive subjects: Prevention of an adverse impact in those at high risk☆

In this work-site population, the illness absenteeism of 259 hypertensive subjects was studied in the year after they were screened and labelled. Absenteeism due to illness increased more in 48 patients who were unaware of their hypertension (newly labelled) than in the 211 subjects who were aware. Among the newly labelled subjects, only the young subjects and those with pure systolic hypertension experienced increased absenteeism; the older subjects with diastolic hypertension did not. The newly labelled subjects who received active follow-up and treatment with antihypertensive medication had only minimal increases in absenteeism. In contrast, those who received active follow-up without medication, and those who received only episodic follow-up had significantly greater increases. Vigorous efforts are warranted to insure active follow-up and treatment for hypertensive subjects after their condition has been labelled. Caution should be exercised in labelling, however, if no antihypertensive treatment is initiated.