Blood pressure development of the spontaneously hypertensive rat after concurrent manipulations of dietary Ca2+ and Na+. Relation to intestinal Ca2+ fluxes

Abstract

The blood pressure of the spontaneously hypertensive rat (SHR) is influenced by the Ca2+ content of its diet. As the SHR's greater dependence on dietary calcium may reflect a defect in intestinal calcium absorption, we measured in vitro unidirectional Ca2+ flux (J) in the duodenum-jejunum (four segments each) of the SHR (n=6) and the normotensive Wistar-Kyoto rat (WKY; n=6) by a modified Ussing apparatus. Because of the known and postulated interactions between Ca2+ and Na+ in both intestinal and vascular tissue, we assessed in vivo the influence of a concurrent manipulation of Na+ intake (three levels: 0.25%, 0.45%, and 1.0%) on the blood pressure development of SHRs (n=35) and WKYs (n=35), between 6 and 20 wk of age, exposed to three levels of dietary calcium (0.1, 1.0, and 2%). Net calcium flux (J(net)) (mean±SEM) was significantly (P<0.01) lower in the SHR (-2.8±6.3 nmol/cm2·h) than in the WKY (34.6±8.8 nmol/cm2·h). The SHR's decreased J(net) resulted from a significantly (P<0.03) lower mucosa-to-serosa flux (J(m-s)) in the SHR (41.0±5.6 nmol/cm2·h) compared with the J(m-s) of the WKY (70.1±9.1 nmol/cm2·h). Serosa-to-mucosa flux for calcium did not differ between the SHR (43.8±6.6 nmol/cm2·h) and the WKY (35.5±8.0 nmol/cm2·h). The SHR's decreased (P<0.002) J(m-s) was confirmed by additional measurements in SHRs and WKYs. J(m-s) was 36.2±3.7 nmol/cm2·h in the SHRs (n=11) and 64.4±6.7 nmol/cm2·h in the WKYs (n=9). The provision of an increased dietary Ca2+ (2% by weight) and increased Na+ (1%) to the SHR prevented the emergence of hypertension (P<0.001) (mean±SEM systolic blood pressure at 20 wk of age; 135±5 mmHg for the 2% Ca2+, 1% Na+ SHR vs. 164±2 mmHg for the control diet SHR). Ca2+ (0.1%) and Na+ (0.25%) restriction accelerated the SHR's hypertension (192±2 mmHg) (P<0.001) and was associated with higher pressures in the WKY (146±4 mmHg in the restricted WKY vs. 134±4 mmHg in the control WKY). In a parallel group of 24 SHRs and 24 WKYs fed one of three diets (2% Ca2+/1% Na+; 1% Ca2+/0.45% Na+; or 0.1% Ca2+/0.25% Na+), the heart (P<0.05) and kidney (P=0.08) weight of the SHRs varied depending on the diet at 20 wk of age. Low Ca2+ and Na+ intake was associated with increased heart weight (1.6±0.9 g) compared with the normal diet for SHR (1.51±0.07 g). Increased Ca2+ and Na+ intake was associated with a significantly (P=0.05) lower heart weight in the SHR (1.37±0.03 g) and in the WKY (1.35±0.06 g) compared with their normal diet controls. These findings show one mechanism for the SHR's depressor response to supplemental dietary Ca2+ and, in part, explain the sodium dependence of calcium's cardiovascular protective effect.