Effects of bosentan and losartan on 2k1c hypertensive rats

Abdulla Upsala Journal of Medical Sciences. On day 8, the rats were anaesthetized, and renal vasoconstrictor experiments were carried out. A group of rats was subjected to acute unilateral renal denervation during the acute study. Data suggest that the renal sympathetic nerve contributes to adrenergic agonist-mediated renal vasoconstrictions in normal rats.

Effects of bosentan and losartan on 2k1c hypertensive rats

Inhibition of PDE5 by sildenafil has been shown to increase endothelial function and decrease blood pressure in experimental models. However, no available study evaluated the baroreflex sensitivity nor autonomic balance in renovascular hypertensive rats treated with sildenafil.

In a translational medicine perspective, our hypothesis is that sildenafil could improve autonomic imbalance and baroreflex sensitivity, contributing to lower blood pressure. At the end of treatment, BP and heart rate HR were recorded in conscious rats after a h-recovery period.

Spontaneous and drug-induced baroreflex sensitivity and autonomic tone were evaluated; in addition, lipid peroxidation was measured in plasma samples. Treatment was efficient in increasing both spontaneous and induced baroreflex sensitivity in treated hypertensive animals.

Inhibition of PDE5 was also capable of ameliorating autonomic imbalance in 2K1C rats and decreasing systemic oxidative stress. Taken together, these beneficial effects resulted in significant reductions in BP without affecting HR.

We suggest that sildenafil could be considered as a promising alternative to treat resistant hypertension.

Effects of bosentan and losartan on 2k1c hypertensive rats

Introduction Even though arterial hypertension is the most common modifiable risk factor for cardiovascular diseases, it is still an important health problem worldwide. Stenosis of renal artery is frequently associated with resistant hypertension. In those patients, the usually available antihypertensive drugs protocol fail to normalize blood pressure BPeven when in association Faselis et al.

Therefore, the urgency in developing new approaches to treat arterial hypertension is clear. The experimental model of renovascular hypertension proposed by Goldblatt mimics human renovascular hypertension Goldblatt et al.

In that model, known as 2-kidneyclip 2K1C model, the unilateral renal artery stenosis reduces renal perfusion and chronically stimulates the renin-angiotensin-aldosterone system RAAS; Navar et al. Several studies describe that the central control of BP is impaired during hypertension in humans and animal models, possibly due to autonomic dysfunction Irigoyen and Krieger, ; Campagnaro et al.

The activation of type 1 Ang II receptor AT1R and the consequent production of reactive oxygen species ROS on different brain nuclei involved in autonomic control are currently well-accepted mechanisms for explaining autonomic dysfunction observed in arterial hypertension Braga et al.

In recent studies, our group and others have shown that antioxidant therapy can reverse the reduced baroreflex sensitivity in spontaneously hypertensive rats SHR and in renovascular hypertensive rats Nishi et al.

Sildenafil is a specific inhibitor of phosphodiesterase 5 PDE5the enzyme responsible for degrading cyclic guanosine monophosphate cGMP. In addition, our group has recently shown that sildenafil exhibits antioxidant properties Balarini et al. However, the efficacy of sildenafil in ameliorating central control of BP during arterial hypertension has not been investigated.

In the present study, we aimed to evaluate the possible effects of sildenafil treatment on the central control of blood pressure through baroreflex sensitivity in 2K1C hypertensive rats. Furthermore, we evaluated whether the treatment was able to improve autonomic imbalance by reducing oxidative stress in those animals.

Materials and Methods Animals Thirty eight Wistar rats Rattus norvegicus weighing — g were used.

Effects of bosentan and losartan on 2k1c hypertensive rats

Study Design Animals were divided in four different groups: Sildenafil dose was chosen based on previous studies and on the difference on pharmacokinetics for sildenafil in different species Walker et al.

Baseline blood pressure BP and heart rate HRbaroreflex function and autonomic tone evaluation test were performed in most of the animals for each group, including the ones used for typical raw tracings representation.

Firstly, baseline BP and HR were recorded for 40 min. For drug-induced baroreflex function studies, phenylephrine and sodium nitroprusside were randomly administered with 15 min interval between doses in order to guarantee that cardiovascular parameters were back to baseline values.

TRPM8 downregulation by angiotensin II in vascular smooth muscle cells is involved in hypertension

Lastly, propranolol and atropine were randomly administered with 3 h interval between doses. Details are given in specific protocols ahead. Body weight and cardiovascular baseline values for each experimental protocol is shown in Table 1 and Table 2respectively.

Weight values from the different groups. Renal Artery Clipping The induction of renovascular hypertension was performed as previously standardized in our laboratory Botelho-Ono et al.

The surgical procedures were executed only after the absence of withdraw and corneal reflexes. Right renal artery was carefully exposed through a retroperitoneal incision.

A U-shaped silver clip 0. Sham animals underwent the same surgical process, except for the implantation of the silver clip.Tracleer is a medicine to treat pulmonary arterial hypertension, which is high blood pressure in the lung arteries.

You take it by mouth. Tracleer can improve your ability to exercise and can slow the worsening of your physical condition and symptoms. Losartan Cozaar Side Effects, Important Info, How to Take.

Successful treatment of hypertension is difficult despite the availability of several classes of antihypertensive drug and strategies to tackle the effect of adverse lifestyle behaviours on blood pressure.

5–30% of the overall hypertensive population have resistant hypertension. Microinjection of the AT1 receptor antagonist, losartan, did not alter the hypotensive effect of angiotensin-(1–7) or alamandine in both groups. These results provide new insights about the differential mechanisms participating in the central cardiovascular effects of alamandine and angiotensin-(1–7) in normotensive and 2K1C hypertensive rats.

Hemodynamic and renal effects of bosentan and losartan in 2k1c hypertensive rats Sarkawt Hamad1* & Ismail Maulood2 1 Biology Department, Faculty of Science, Soran University, Soran, Iraq;. Two-kidney, one-clip (2K1C) renovascular hypertensive rats were assigned to sedentary (Sed) or treadmill running groups for eight weeks.

Dizocilpine (MK), a glutamate receptor blocker, or losartan (Los), an angiotensin II type1 receptor (AT1-R) blocker, were microinjected into the PVN at .