SUMMARY Disorders of calcium metabolism are not generally considered important either clinically or patbophysiologkally in essential hypertension. Recent reports, though, suggest that increased parathyroid gland function may be one of the more common endocrine disturbances associated with hypertension. We measured serum parathyroid hormone (PTH) concentrations as well as routine blood and arine chemistries in 34 hypertensives. Their mean PTH, 79.1 ± 3.1 filter Eq/ziUter, was rignlflcaatiy higher {p < 0.025) than the mean PTH, 66.9 ± 33, of an age-and sex-matched nonnotenshe control population. The mean serum calcium, 9.5 ± 0.1 mg%, was identical in the two populations. Compared to a second age-aad sex-matched normotensive population, the hypertensives demonstrated a significant (p < 0.005) relatiTe hypercalduria. For any lerd of urinary sodium, hypertenshes excreted more calcium. These preliminary data suggest that parathyroid gland function may be enhanced in essential hypertension. This increased gland actirity appears, in part, to be an appropriate, physiologic response to a previously unrecognized relative hypercalduria, or renal caldum leak, associated with essential hypertension. We condude that the increased prevalence of hypertension in subjects with byperparathyroidfam probably represents the final event In a continuum that begins with obligatory urinary caldum losses in hypertensives, but whose pathological presentation is hyperparathyroidism. The results of this pilot study indicate a need for derivative experiments directed at defining the importance of our preliminary findings In the patbogenesis of human and experimental hypertension. 1 "' Conversely, the prevalence of hyperparathyroidism may be two to eight times greater in hypertensive than in normotensive subjects. 4-• In addition, thiazide diuretics cause overt hypercalcemia in certain hyper-

Ionized calcium is critical to the maintenance of normal cardiovascular function. Recently, vasoactive properties have also been attributed to parathyroid hormone (PTH). The present study characterizes the calcium-PTH axis in the spontaneously hypertensive rat (SHR) in order to determine the effects of chronic alterations in calcium intake on the development and maintenance of hypertension in this species. Thirty-six SHR and 36 Wistar-Kyoto (WKY) normotensive control rats were studied. The rats were fed one of three levels (percent of total diet) of calcium (normal 0.5%, low-normal 0.25%, high 4.0%) beginning at 10 weeks of age. Serum total and ionized calcium, serum PTHs, urinary electrolytes, and systolic blood pressures were assessed by repeated measurements between 10 and 48 weeks of age. Irrespective of calcium intake, the SHRs had lower serum ionized calcium concentrations (p less than 0.001) and higher PTH levels (p less than 0.001) than the WKYs. Serum total calcium were similar for the two strains. Urinary calcium excretion was greater in the SHR (p less than 0.001) relative to the WKY. The high (4.0%) calcium diet normalized the serum ionized calcium and attenuated the development of the SHRs' hypertension (p less than 0.001). The present study describes several previously unrecognized abnormalities of calcium metabolism in the SHR. These disturbances may be of pathogenetic importance in the development and maintenance of hypertension in the SHR.

To elucidate the relationship between the renal regulation of sodium and calcium excretion at extremes of sodium intake, we studied 6 normal men ingesting a fixed, 400 mg/day calcium intake and four levels of sodium intake from 10 to 1,500 mEq/day. Serum ionized calcium was not influenced by sodium intake. Blood pressure and cardiac index increased modestly. Urinary calcium excretion increased to 262 ± 53 mg/day (mean ± SE). Plasma norepinephrine concentration, serum PTH levels, hematocrit, total serum protein concentrations and CO₂ content decreased with increasing sodium intake. Urinary cAMP increased as sodium intake was raised from 10 to 300 mEq/day, but subsequently decreased to basal values. Urinary calcium and sodium excretion were related (p < 0.001) in a nonlinear fashion as were the fractional excretions of these cations (p < 0.001). The filtered calcium load and the fractional calcium excretion were directly and linearly related (p < 0.001). We conclude that the effect of sodium intake on urinary calcium excretion principally reflects changes in the filtered calcium load rather than changes in renal sodium handling. Calcium homeostasis at extremes of sodium intake does not appear to be critically dependent upon PTH-mediated mechanisms. The data suggest that the proximal tubule has a remarkable capacity to dissociate calcium resorption from that of sodium.