ABSTRACT
Spontaneously hypertensive rats have long been used as an animal counterpart of human essential hypertension. The validation of this strain as a model rests mainly on the "clinical" similarity of the two syndromes, but it has scarcely been founded on numerical comparison of measurable parameters. We investigated three hematological indexes previously recognized to be altered in spontaneously hypertensive rats: the single-cell volume of erythrocytes, the single-cell volume of platelets, and the erythrocyte number. Erythrocyte volume was lower by 7%, platelet volume was higher by 12%, and erythrocyte count was higher by 22% in spontaneously hypertensive rats in comparison with Wistar-Kyoto controls. More unexpectedly, it was found that erythrocyte volume is lower by 2%, platelet volume is higher by 3%, and erythrocyte number is higher by 6% in essential hypertensive subjects when compared with normotensive healthy subjects. These results, combined with previously reported blood cell alterations in subjects and rats, reinforce the evidence of a biological similarity between essential and spontaneous hypertension.
Subject(s)
Disease Models, Animal , Hypertension/blood , Rats, Inbred Strains/blood , Rats, Inbred WKY/blood , Animals , Erythrocyte Count , Erythrocyte Volume , Female , Humans , Male , Platelet Count , RatsABSTRACT
H3-dihydroalprenolol (H3-DHA) binding in isolated smooth muscle cells has been studied. Two different binding sites have been detected: a high affinity (highly specific) and a low affinity (nonspecific) binding site. Local anaesthetics are able to displace H3-DHA from nonspecific sites with a rank order of potency that mirrors their local anaesthetic activity. This finding correlates, at the molecular level, with the local anaesthetic properties of beta-blockers, as concluded from classical pharmacological experiments.
Subject(s)
Adrenergic beta-Antagonists/pharmacology , Anesthetics, Local/metabolism , Receptors, Drug/metabolism , Animals , Dihydroalprenolol , In Vitro Techniques , Kinetics , Male , Muscle, Smooth, Vascular/drug effects , Rats , Rats, Inbred StrainsABSTRACT
Diminished beta-adrenoceptor mediated relaxation and increased reactivity to norepinephrine have been observed in the arteries of spontaneously hypertensive rats (SHR). However, some reports are conflicting, while the complexity of endothelial, neural and purely morphological factors regulating the response of whole vessels is increasingly appreciated. Thus a dissection of the complex vascular contraction mechanism into single-step events is needed. Here characterization of adrenoceptors in isolated aortic smooth muscle cells of SHR by radioligand binding techniques is reported. The density of beta-adrenoceptors was decreased at 4 (-23%), 7(-20%) and 13(-39%) weeks in SHR compared with age-matched normotensive Wistar-Kyoto rats. In both strains beta-adrenoceptor density decreased significantly with age. alpha 1-Adrenoceptors exhibited complex, though slight, changes in SHR at different ages. The alpha/beta adrenoceptor density ratio was constantly increased in SHR (11.9 versus 7.6 at 7 weeks; 19.1 versus 15.8 at 13 weeks). These findings suggest that the abnormal contractility of SHR arteries may at least partially depend on changes at the adrenoceptor level. A loss of arterial beta-adrenoceptors early in the life of SHR can be an event leading to increased peripheral resistance and elevation of blood pressure.
