cytochalasin-b and Hypertension

The influence of passive tension on contractions to phorbol 12,13-dibutyrate (1 microM PBDu) on the thoracic aorta of Wistar and SHR rats, aged 8-12 weeks, and the functional importance of both the actin and the tubulin components of the cytoskeleton, were studied. Contractile responses to PBDu (1 microM) were obtained in aorta rings, at two levels of passive tension: 3 and 0.5g. These responses were expressed as percentage of the maximal response to noradrenaline obtained in the beginning of the experiment at a tension of 2g. Responses to PBDu were significantly larger (P<0.05) at 3g than at 0.5g in both kinds of rats: 226.5+/-34.4%, n=6, versus 143.0+/-28.5%, n=6, respectively, for SHR; 153.0+/-12.9%, n=8, versus 109.0+/-7.3%, n=7, respectively, for Wistar rats. Responses to PBDu were markedly decreased by cytochalasin B (50 microM) (to 61.3+/-14.3%, n=6, at 3g, and 29.6+/-17.8%, n=5, at 0.5g in SHR; to 18.5+/-0.9%, n=6, at 3g, and 6.4+/-1.8%, n=5, at 0.5g in Wistar rats). Colchicine (100 microM) failed to produce a decrease in responses to PBDu in both strains of rats. It is concluded that responses to phorbol ester action depend on passive tension. This difference may depend on filament interaction. Contractions to PBDu in the rat aorta may be highly dependent on actin polymerization.

Topics: Actins; Animals; Aorta, Thoracic; Body Weight; Colchicine; Cytochalasin B; Cytoskeleton; Hypertension; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth, Vascular; Phorbol 12,13-Dibutyrate; Protein Kinase C; Rats; Rats, Inbred SHR; Rats, Wistar; Tubulin Modulators

D-fructose transport was characterized in renal brush-border membrane vesicles (BBMVs) from both spontaneously hypertensive rats (SHR) and normotensive genetic control Wistar-Kyoto (WKY) rats. Kinetic studies indicated that the maximal rate (Vmax) of D-fructose transport was significantly lower in SHR compared with WKY rats. No differences were observed in the Michaelis constant (Km) or the diffusion constant (Kd) between the two groups of animals. D-fructose inhibited its own transport, whereas the presence of D-glucose, D-galactose, phlorizin, and cytochalasin B did not inhibit the transport of D-fructose in either animal group. To explain the reduction in D-fructose transport in SHR, the density of the D-fructose transporter, GLUT5, was analyzed by Western blot. GLUT5 levels were lower in SHR, a reduction similar to that of the Vmax. Thus, there appears to be a high-affinity, low-capacity, GLUT5-type fructose carrier in the apical membranes of rat kidney cortex, and the decrease in the Vmax of D-fructose transport in renal BBMVs from hypertensive rats correlates well with a reduction in the expression of GLUT5 protein.

Topics: Animals; Biological Transport; Blood Pressure; Body Weight; Cytochalasin B; Fructose; Galactose; Glucose; Glucose Transporter Type 5; Hypertension; Immunoblotting; Kidney; Male; Microvilli; Monosaccharide Transport Proteins; Phlorhizin; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium; Transport Vesicles

1. The present study aimed at comparing the influence of passive tension on the effect exerted by noradrenaline on the thoracic aorta of 6-month-old Wistar and spontaneously hypertensive rats (SHR). 2. Concentration-response curves to noradrenaline were obtained in aorta rings, at two levels of passive tension: 3 and 0.5 g. 3. The maximal responses (in percentage of the maximal response to noradrenaline obtained in the beginning of the experiment at a tension of 2 g) were significantly larger (P < 0.05) at 3 g than at 0.5 g in both kinds of rats: 171 versus 69%, respectively, for SHR; 139 versus 76%, respectively, for Wistar rats. 4. When expressed as mg of active tension per mg of tissue, the maximal contraction at both 3 and 0.5 g was smaller in SHR than in Wistar rats (at 3 g: 64.6 +/- 6.7, n = 6 versus 122.3 +/- 19.1, n = 8, respectively, P < 0.05; at 0.5 g: 24.0 +/- 1.0, n = 6 versus 49.0 +/- 5.9, n = 8, respectively, P < 0.05). 5. Maximal responses to noradrenaline were markedly decreased by cytochalasin B (50 microM) (to 15.2 +/- 6.0%, n = 6, at 3 g and 2.8 +/- 1.9%, n = 6, at 0.5 g in SHR; to 11.8 +/- 2.3%, n = 4, at 3 g and 4.3 +/- 1.3%, n = 4, at 0.5 g in Wistar rats). Cytochalasin B at a lower concentration (4 microM) produced a less marked decrease in responses to noradrenaline in both strains of rats. The presence of cardiovascular structural changes in SHR was confirmed by the fact that the heart weight (mg):body weight (g) was higher in SHR (3.37 +/- 0.06, n = 10) than in Wistar rats (2.40 +/- 0.12, n = 11) (P < 0.05). 6. It is concluded that in 6-month-old SHR the contractile capacity of the aortic tissue is reduced. However, the differential sensitivity of aortic smooth muscle at the two different levels of tension remains present. This difference may depend on filament interaction. Contractions to noradrenaline in the rat aorta are highly dependent on actin polymerization.

Topics: Animals; Aorta, Thoracic; Body Weight; Cytochalasin B; Hypertension; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Organ Size; Rats; Rats, Inbred SHR; Rats, Wistar; Vasoconstrictor Agents