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OBJECTIVE To investigate whether the reported association between insulin resistance and hypertension in spontaneously hypertensive rats (SHR) is a primary defect or a secondary phenomenon in hypertension. DESIGN Comparisons of glucose metabolism between three groups of hypertensive rats: deoxycorticosterone (DOCA)-salt hypertensive rats; two-kidney, one clip renovascular hypertensive (RVH) rats; SHR; and their respective control groups. There was also an additional group of weight-matched SHR and respective Wistar-Kyoto (WKY) controls. METHODS A trace amount of 3H-deoxyglucose (3H-DOG) was administered in vivo to evaluate its plasma half-life and tissue uptake. In vitro adipose tissue segments were incubated with 14C-glucose and increasing doses of insulin. RESULTS Compared with age-matched WKY rats, SHR had significantly higher insulin levels, longer plasma half-life and lower 3H-DOG uptake by heart and striated muscle. Plasma glucose levels and incorporation of 14C-glucose into CO2, triglycerides and glycogen by adipose tissue in response to increasing insulin concentrations was similar for both groups of SHR and WKY rats. No differences were found between hypertensive rats and controls in either the DOCA or RVH groups. CONCLUSION Evidence of insulin resistance in spontaneous, but not secondary, rat hypertension indicates that the resistance is a primary rather than a secondary event in hypertension.

The metabolism of phosphoinositides, a class of membrane lipids involved in Ca2+ -transport and/or mobilization systems was investigated in patients with moderate essential hypertension and in Sabra rats. Experiments were performed in vitro on isolated erythrocyte membranes by measuring the 32P-labelling of phosphatidylinositol 4,5-bisphosphate (PI-P2) and of phosphatidylinositol 4-phosphate (PI-P) following the incubation of membranes with [gamma-32P] ATP. In untreated essential hypertensives (n = 31) or in hypertensive patients whose blood pressure was controlled by beta-blocker therapy (n = 20), 32P-PI-P2 was significantly higher than in normotensive controls (n = 30); no significant difference was observed between the two groups of hypertensive patients. In Sabra rats fed on a low Na diet, 32P-PI-P2 levels were significantly higher in hypertensive-prone animals (SBH) than in hypertensive-resistant animals (SBN). When the animals were fed a high Na diet or were DOCA/salt treated, 32P-PI-P2 did not change in either substrain, although such conditions differentially affected the blood pressure of SBH and SBN. Our data indicate that the modification of phosphoinositide metabolism is not a consequence of the blood pressure elevation, but can be considered as an intrinsic membrane defect which may be associated with functional alterations of Ca2+ fluxes which in hypertensives result in an enhanced intracellular Ca2+ level.

Cerebral and renal alpha 2-adrenoceptors are implicated in the control of sympathetic activity and of sodium reabsorption respectively. In addition, sodium ions play an important role in the regulation of either alpha 2-adrenoceptor densities and affinities for adrenergic agonists. In the present study, alpha-adrenoceptor properties were investigated in genetically predetermined salt-sensitive and salt-resistant Dahl and Sabra rats. Cerebral alpha 2-adrenoceptor densities were higher in salt-resistant than in salt-sensitive Dahl and Sabra rats. In contrast, renal alpha 2-adrenoceptor density was higher in salt-sensitive than in salt-resistant rats. No difference in cerebral and renal alpha 1-adrenoceptor densities was observed between Dahl and Sabra substrains. Noradrenaline content in cerebral and renal cortex were also similar in both these rat substrains. Sodium ions markedly increased cerebral and renal high-affinity alpha 2-adrenoceptor densities in salt-sensitive but not in salt-resistant rats. Cerebral and renal alpha 1-adrenoceptor densities were unchanged in salt-sensitive and salt-resistant substrains of Dahl and Sabra rats. In addition, sodium ions reduced the affinity of adrenaline for renal alpha 2-adrenoceptors in salt-sensitive rats but not in salt-resistant rats. We can conclude that there exist genetically determined differences in the densities and properties of cerebral and renal alpha 2-adrenoceptors between salt-sensitive and salt-resistant rat strains. Abnormal densities of alpha 2-adrenoceptors may play a primary role in the role in the development of hypertension in salt-sensitive animals. These results also suggest an association between absence of sodium regulation of alpha 2-adrenoceptors and resistance to salt-induced hypertension. The absence of sodium regulation in salt-resistant rats may be linked either to a particular receptor conformation or to an abnormal structure of the receptor system. This property may represent a genetically-mediated change responsible for the resistance to the development of salt-induced hypertension.

1. The clinical applications of a simple laboratory test for the diagnosis of essential hypertension were further investigated on a large number of patients (124 individuals). 2. The reduced erythrocyte ratio of Na+/K+ net fluxes observed in essential hypertensives might be secondary to a functional defect in a Na+—K+ co-transport system. 3. A similar reduction in the ratio of Na+/K+ net fluxes was also observed in erythrocytes of some normotensive subjects born of hypertensive parents and of genetically hypertensive rats. This suggests that the erythrocyte membrane defect follows the genetic transmission of hypertension.

Sodium ions play an important role in vitro and in vivo in the regulation of alpha 2-adrenoceptors. The in vitro effect of sodium on cerebral and renal alpha-adrenoceptors was investigated in Dahl salt-sensitive and salt-resistant rats. Cerebral alpha 2-adrenoceptor densities were higher in Dahl salt-resistant rats. In contrast, the renal alpha 2-adrenoceptor density was higher in Dahl salt-sensitive than in Dahl salt-resistant rats. No difference in cerebral and renal alpha 1-adrenoceptor densities was observed between the two types of rat. Noradrenaline contents in the cerebral and renal cortex were also similar in these two rat substrains. An influx of sodium ions markedly increased cerebral and renal high-affinity alpha 2-adrenoceptor densities in Dahl salt-sensitive but not in Dahl salt-resistant rats. Under these conditions alpha 1-adrenoceptor densities remained unchanged. The absence of sodium regulation in Dahl salt-resistant rats may be linked either to a particular receptor conformation or to an abnormal structure of the alpha 2-adrenoceptor system. We conclude from the present study that there are marked differences in density and in the role of sodium regulation of cerebral and renal alpha 2-adrenoceptors from salt-sensitive and salt-resistant Dahl rats. These differences may play a primary role in the resistance or in the sensitivity of salt-induced hypertension.