Spice up the hypertension diet - curcumin and piperine prevent remodeling of aorta in experimental L-NAME induced hypertension

Abstract

Background: Increase of blood pressure is accompanied by functional and morphological changes in the vascular wall. The presented study explored the effects of curcuma and black pepper compounds on increased blood pressure and remodeling of aorta in the rat model of experimental NO-deficient hypertension.

Methods: Wistar rats were administered for 6 weeks clear water or L-NAME (40 mg/kg/day) dissolved in water, piperine (20 mg/kg/day), curcumin (100 mg/kg/day) or their combination in corn oil by oral gavage. The systolic blood pressure was measured weekly. Histological slices of thoracic aorta were stained with hematoxylin and eosin, Mallory's phosphotungstic acid hematoxylin (PTAH), orcein, picrosirius red and van Gieson staining and with antibodies against smooth muscle cells actin. Microscopic pictures were digitally processed and morphometrically evaluated.

Results: The increase of blood pressure caused by L-NAME was partially prevented by piperine and curcumin, but the effect of their combination was less significant. Animals with hypertension had increased wall thickness and cross-sectional area of the aorta, accompanied by relative increase of PTAH positive myofibrils and decrease of elastin, collagen and actin content. Piperine was able to decrease the content of myofibrils and slightly increase actin, while curcumin also prevented elastin decrease. The combination of spices had similar effects on aortic morphology as curcumin itself.

Conclusions: Administration of piperine or curcumin, less their combination, is able to partially prevent the increase of blood pressure caused by chronic L-NAME administration. The spices modify the remodeling of the wall of the aorta induced by hypertension. Our results show that independent administration of curcumin is more effective in preventing negative changes in blood vessel morphology accompanying hypertensive disease.

Figure 1

Effect of piperine and curcumin on systolic blood pressure in L-NAME-induced hypertension. Con - control, L - L-NAME induced hypertension, P - piperine, C - curcumin. + p < 0.05, ++ p < 0.01, +++ p < 0.001 versus L.

Figure 2

Changes in cross sectional area (CSA) of the media of aorta induced by hypertension and the effect of piperine and curcumin in the graphic form (left) and examples of the aorta stained with hematoxylin and eosin (right). Con - control, L - L-NAME induced hypertension, P - piperine, C - curcumin. * p < 0.05 versus Con, ++ p < 0.01 versus L.

Figure 3

The absolute amount of myofibrils in the aortic media identified with phosphotungstic acid hematoxylin was significantly increased in hypertensive animals (L), curcumin caused their return to the level of controls. Graphic form of the results (left) obtained from aorta specimens stained with PTAH (right). CSA - cross sectional area, Con - control, L - L-NAME induced hypertension, P - piperine, C - curcumin. +++ p < 0.001 versus L, . *** p < 0.001 versus Con.

Figure 4

Smooth muscle cell actin in the media of aorta was decreased in hypertensive animals, both spices substances reversed this decrease. Immunohistochemical detection of smooth muscle actin (right) and evaluation in graphic form (left). CSA - cross sectional area, Con - control, L - L-NAME induced hypertension, P - piperine, C - curcumin. ++ p < 0.01 versus L,+++ p < 0.001 versus L, ** p < 0.01 versus Con, *** p < 0.001 versus Con.

Figure 5

The total content of collagen in the aorta was significantly decreased in hypertensive animals. The spices did not substantially correct this drop. Graph (left) with results from van Gieson staining, specimens stained with picrosirius red evaluated in polarized light (right). Con - control, L - L-NAME induced hypertension, P - piperine, C - curcumin. ** p < 0.01 versus Con, *** p < 0.001 versus Con.

Figure 6

Content of elastin in the aortic media was significantly increased in animals with hypertension, the spices induced its further raise. Graphic form of the results (left) obtained from aorta specimens stained with orcein (right). CSA - cross sectional area, Con - control, L - L-NAME induced hypertension, P - piperine, C - curcumin. + p < 0.05 versus L,+++ p < 0.001 versus L, ** p < 0.01 versus Con, *** p < 0.001 versus Con.

Figure 7

The amount of the ground substance of the aorta was increased in animals with L-NAME-induced hypertension and this increase was reduced by both piperine and by curcumin, more effectively in their combination. Con - control, L - L-NAME induced hypertension, P - piperine, C - curcumin.