The role of calcium sensitization and calcium influx in the regulation of  blood pressure and sympathetic vasoconstriction in conscious normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR)

Blood pressure is dependent on cardiac output and peripheral resistance, which is dependent on vascular tone. The concept of calcium influx into the smooth muscle cells as the main parameter controlling vascular tone has been extended recently on another pathway, namely Rho-kinase. This pathway enables the prolongation of short-term vasoconstriction elicited by increased calcium influx. Our recent study in the prestigious Journal of Hypertension contributed to the highlighting of the participation of Rho-kinase pathway in blood pressure regulation in spontaneously hypertensive rats and their normotensive WKY controls.  

Behuliak M et al: Ca²⁺ sensitization and Ca²⁺ entry in the control of blood pressure and adrenergic vasoconstriction in conscious Wistar-Kyoto and spontaneously hypertensive rats. Journal of Hypertension 2013, 31:2025-2035

The role of endothelin system in the regulation of blood pressure in rats with different forms of experimental hypertension on high salt intake

Endothelin is a very potent vasoconstrictor. The role of endothelin (ET) receptor blockade was evaluated in salt-sensitive (Dahl-S) rats with salt hypertension. We found that the mechanisms of endothelin receptor blockade are different in young and adult animals with salt-sensitive hypertension. Blockade of ET_A receptor lowered blood pressure in adult Dahl-S rats, while it had no antihypertensive effect in young animals. The antihypertensive effect of chronic ET_A receptor blockade in adult rats was mediated by the inhibition of sympathetic vasoconstriction.

Zicha J et al: Chronic endothelin A receptor blockade attenuates contribution of sympathetic nervous system to salt hypertension development in adult but not in young Dahl rats, Acta Physiologica 2012, 205: 124-132

Following project was solved in collaboration with the colleagues from the Institute for Clinical and Experimental Medicine in Prague. In a model of renal failure induced by the partial nephrectomy, we studied whether the addition of endothelin receptor blockade to the classical renin-angiotensin blockade, could have some beneficial, especially nephroprotective effects. Although ET_A receptor blockade alone partially increased survival of animals, moderately lowered BP and transiently decreased proteinuria, no additional beneficial cardiorenal effects of such blockade were found.  

Vaněčková I et al: Effects of combined endothelin A receptor and Renin-Angiotensin system blockade on the course of end-organ damage in 5/6 nephrectomized Ren-2 hypertensive rats. Kidney Blood Pressure Research, 2012, 35:382-392

The role of reactive oxygen species in hypertension

It is well-known that reactive oxygen species (ROS) participate at origin or development of different diseases. In our study, we analyzed the effects of ROS in a model of salt hypertension in Dahl salt-sensitive (Dahl-S) rats. Our results showed that ROS have different effects in young and adult animals. While antioxidant therapy with tempol lowered blood pressure in adult animals (by reduction of sympathetic vasoconstriction), it had no effect in young ones. High-salt diet substantially reduced the NO synthase activity in heart and kidney, and markedly increased superoxide production in kidneys and aorta of adult Dahl-S rat on high-salt diet.

VaněčkováI  et al: Chronic antioxidant therapy lowers blood pressure in adult but not in young Dahl salt hypertensive rats: the role of sympathetic nervous system, Acta Physiologica 2013, 208: 340-349