We investigated the role of altered vascular calcium handling in the development of aldosterone-salt hypertension in the rat. The calcium sensitivity of isometric force in response to 50 mM KCl was compared in aortic rings from control and aldosterone-hypertensive rats. Over the entire range of calcium concentrations studied, responses in aortas from the hypertensives were significantly depressed compared to controls [ED50: aldosterone-hypertensive rats (n = 6), 0.739 +/- 0.137; controls (n = 7), 0.141 +/- 0.021 mM; P less than 0.001]. However, calcium sensitivity in response to 1 microM norepinephrine was similar in aortas from both hypertensives and controls [ED50: aldosterone-hypertensive rats (n = 7), 0.196 +/- 0.022; controls (n = 7), 0.180 +/- 0.024 mM]. The calcium sensitivity of Triton X-100 skinned aortic rings from aldosterone-hypertensive rats was likewise not significantly different from sensitivity in controls [ED50: aldosterone-hypertensive rats (n = 9), 3.61 X 10(-7) +/- 0.57; controls (n = 8), 3.89 X 10(-7) +/- 0.64 M]. Therefore, the observed decrease in calcium sensitivity in response to membrane depolarization in aortas from aldosterone-hypertensive rats probably is not due to a change in calcium sensitivity of the contractile system itself. The time course for development of changes in calcium handling in vessels from the aldosterone-hypertensive rats was found to be quite different from the time course for changes in monovalent ion metabolism. Whereas increases in monovalent ion permeability reportedly appear as early as one week after the start of aldosterone-salt treatment, significant alterations in calcium handling were not apparent until after four weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortas from aldosterone-salt treated hypertensive rats and vehicle-infused normotensive controls were compared with respect to mechanical properties, metabolism, and energy turnover. Passive wall stress at any given circumference was slightly higher in aortas from the hypertensive rats, whereas active isometric force normalized to cross-sectional area was similar in vessels from the two groups at their respective optimal circumference for active tension developments [hypertensive rats: (n = 14), 19.73 +/- 1.98; controls: (n = 13), 22.57 +/- 2.13 mN/mm2). Metabolic parameters were measured with the aortas held at optimal circumference for active tension development, the optimal length for tension development (n = 6), 5.67 +/- 0.17 and (n = 7), 5.29 +/- 0.18 mm for control and aldosterone-salt groups, respectively. Basal oxygen consumption rate was elevated significantly in aortas from the hypertensive rats [(n = 14), 0.457 +/- 0.026 vs. (n = 13), 0.267 +/- 0.028 mumol/min per g; P less than 0.001]. Under resting conditions, lactate production rate similar in aortas from the two groups [hypertensive rats: (n = 20), 0.129 +/- 0.010; controls: (n = 21), 0.112 +/- 0.008 mumol/min per g]. Upon activation with added KCl, the rate of oxygen consumption and lactate production increased with tension development in both groups, but the stimulated rate of oxygen consumption was higher in hypertensives compared to controls [(n = 14), 0.580 +/- 0.031 vs. (n = 13), 0.441 +/- 0.049 mumol/min per g; P less than 0.025]. The stimulated rates of lactate production were similar in the two groups [hypertensive rats: (n = 20), 0.172 +/- 0.009; controls: (n = 21), 0.118 +/- 0.009].(ABSTRACT TRUNCATED AT 250 WORDS)

Studies have been conducted to determine which, if any, of the parameters governing active Na-K transport (K and/or ouabain sensitive) are altered in vascular smooth muscle during mineralocorticoid-salt hypertension. Rats with one kidney removed were treated with either aldosterone or deoxycorticosterone acetate plus saline for 3-4 wk. Ion transport was measured in arteries incubated in a physiological salt solution for periods of 4-6 h. Increased active Na efflux was observed in femoral arteries and aortas from the hypertensive group. This alteration resulted primarily from an elevation in the saturation or maximal capacity of the active transport mechanism, which operated with no significant change in cell Na concentration. The transport parameters related to ion selectivity, cooperativity, and temperature dependence were not significantly altered. Measures of active Na efflux and K influx in the same aortic strips indicated that both fluxes were elevated in the hypertensive group. The ratio of Na to K for active transport was significantly greater than one but was unchanged in the hypertensive rats. These studies provide evidence for the electrogenic operation of the Na-K pump in arterial smooth muscle and for the operation of the pump at a higher level during mineralocorticoid-salt hypertension. This alteration may result from increased turnover of individual sites or possibly the incorporation of more sites into the membrane as a result of mineralocorticoid-salt treatment.

The present study was undertaken to determine the extent to which cyclic nucleotide-induced relaxation in the intact rat aorta is mediated at the level of the contractile system. The relaxant effects of the cyclic nucleotide analogues [8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) and dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP)] and forskolin were examined in both the intact vessel and a Triton X-100-skinned preparation of rat thoracic aorta. Relaxation of a norepinephrine-induced contraction was essentially complete 30 min after the addition of 50 microM 8-BrcGMP [% relaxation = 87.2 +/- 4.4% (n = 4)], 100 microM DBcAMP [98.2 +/- 1.2% (n = 4)], and 1 microM forskolin [107.0 +/- 3.3% (n = 5)]. These same doses were ineffective in relaxing precontracted skinned rat aortic rings compared with the relaxation achieved in the intact vessel. The largest relaxation in the skinned aortas was achieved with the addition of 1 microM forskolin [17.4 +/- 1.5% (n = 4)]. The addition of catalytic subunit of cAMP-dependent protein kinase had no effect on isometric tension in the precontracted skinned aorta. Preincubation with the cyclic nucleotide analogues or forskolin in a low-Ca2+ solution (pCa less than 8) was also ineffective in inhibiting subsequent isometric tension development. Our results suggest that only a very small fraction of the relaxation with cyclic nucleotides and forskolin in the intact rat aorta is due to the action of these agents at the level of the contractile system.

The isomyosin composition in left and right ventricles from aldosterone-salt-treated hypertensive rats and from vehicle-infused and aldosterone-infused normotensive control rats was compared. A significant incremental increase (20%) in the percentage of V3 isomyosin and parallel decrease in the percentage of V1 isomyosin occurred in both left and right ventricles from aldosterone-salt-treated animals compared with those in normotensive vehicle-infused controls. No change in the ventricular isomyosin distribution was observed in animals infused with aldosterone without salt, which indicates that aldosterone does not directly affect the ventricular isomyosin composition. The changes in left ventricular isomyosin composition were accompanied by significant left ventricular hypertrophy (38%; p less than 0.05), whereas no hypertrophy was observed in the right ventricle. Plasma thyroxine levels were significantly lower in aldosterone-salt-treated rats (3.7 +/- 0.6 micrograms/dl; p less than 0.05) than in normotensive vehicle-infused (6.0 +/- 0.7 micrograms/dl) or aldosterone-infused (6.7 +/- 0.3 micrograms/dl) controls. These results indicate that factors such as alterations in thyroid status or a volume overload component of this hypertensive model, in addition to increased systolic blood pressure, may contribute to a biventricular shift in isomyosin composition in the aldosterone-salt model of hypertension.