Voluntary Exercise Prevents Hypertensive Response Sensitization Induced by Angiotensin II.

Exercise training has profound effects on the renin-angiotensin system, inflammatory cytokines and oxidative stress, all of which affect autonomic nervous system activity and regulate blood pressure (BP) in both physiological and pathophysiological states. Using the Induction-Delay-Expression paradigm, our previous studies demonstrated that various challenges (stressors) during Induction resulted in hypertensive response sensitization (HTRS) during Expression. The present study tested whether voluntary exercise would protect against subpressor angiotensin (ANG) II-induced HTRS in rats. Adult male rats were given access to either "blocked" (sedentary rats) or functional running (exercise rats) wheels for 12 weeks, and the Induction-Delay-Expression paradigm was applied for the rats during the last 4 weeks. A subpressor dose of ANG II given during Induction produced an enhanced hypertensive response to a pressor dose of ANG II given during Expression in sedentary rats in comparison to sedentary animals that received saline (vehicle control) during Induction. Voluntary exercise did not attenuate the pressor dose of ANG II-induced hypertension but prevented the expression of HTRS seen in sedentary animals. Moreover, voluntary exercise reduced body weight gain and feed efficiency, abolished the augmented BP reduction after ganglionic blockade, reversed the increased mRNA expression of pro-hypertensive components, and upregulated mRNA expression of antihypertensive components in the lamina terminalis and hypothalamic paraventricular nucleus, two key brain nuclei involved in the control of sympathetic activity and BP regulation. These results indicate that exercise training plays a beneficial role in preventing HTRS and that this is associated with shifting the balance of the brain prohypertensive and antihypertensive pathways in favor of attenuated central activity driving sympathetic outflow and reduced BP.

Controlled Hemorrhage Sensitizes Angiotensin II-Elicited Hypertension through Activation of the Brain Renin-Angiotensin System Independently of Endoplasmic Reticulum Stress.

Hemorrhagic shock is associated with activation of renin-angiotensin system (RAS) and endoplasmic reticulum stress (ERS). Previous studies demonstrated that central RAS activation produced by various challenges sensitizes angiotensin (Ang) II-elicited hypertension and that ERS contributes to the development of neurogenic hypertension. The present study investigated whether controlled hemorrhage could sensitize Ang II-elicited hypertension and whether the brain RAS and ERS mediate this sensitization. Results showed that hemorrhaged (HEM) rats had a significantly enhanced hypertensive response to a slow-pressor infusion of Ang II when compared to sham HEM rats. Treatment with either angiotensin-converting enzyme (ACE) 1 inhibitor, captopril, or ACE2 activator, diminazene, abolished the HEM-induced sensitization of hypertension. Treatment with the ERS agonist, tunicamycin, in sham HEM rats also sensitized Ang II-elicited hypertension. However, blockade of ERS with 4-phenylbutyric acid in HEM rats did not alter HEM-elicited sensitization of hypertension. Either HEM or ERS activation produced a greater reduction in BP after ganglionic blockade, upregulated mRNA and protein expression of ACE1 in the hypothalamic paraventricular nucleus (PVN), and elevated plasma levels of Ang II but reduced mRNA expression of the Ang-(1-7) receptor, Mas-R, and did not alter plasma levels of Ang-(1-7). Treatment with captopril or diminazene, but not phenylbutyric acid, reversed these changes. No treatments had effects on PVN protein expression of the ERS marker glucose-regulated protein 78. The results indicate that controlled hemorrhage sensitizes Ang II-elicited hypertension by augmenting RAS prohypertensive actions and reducing RAS antihypertensive effects in the brain, which is independent of ERS mechanism.

[Changes of protein kinase C activity in experimental presyrinx state in rabbits].

OBJECTIVE: To investigate the changes of protein kinase C (PKC) activity and its role in the development of presyrinx state in rabbits. METHODS: Presyrinx state was established in 56 rabbits by intra-cisternal injection of kaolin. At 1, 3, 7, 14, and 21 days after the injection, the water content in the upper cervical spinal cord was measured, its pathological changes observed microscopically and the PKC activity determined with substrate phosphorolysis kinase assay. RESULTS: Spinal cord edema occurred in rabbits one day after kaolin injection, with water content of (68.35-/+0.70)%, which increased to (72.70-/+0.88)% on day 3, reaching the peak level of (72.92-/+0.86)% on day 7, followed by gradual decline after 3 weeks [(70.03-/+0.77)%]. The membrane PKC activity increased from 5.67-/+0.26 pmol.mg(-1).min(-1) on day 1 after the injection to reach the peak level on day 7 (13.27-/+3.15 pmol.mg(-1).min(-1)), which was maintained till day 14 with subsequent decrease to 8.85-/+1.56 pmol.mg(-1).min(-1) on day 21. The cytoplasmic PKC activity showed changes of a reverse pattern. CONCLUSION: In rabbits with experimental presyrinx state, PKC translocation and activation is involved in ischemic spinal edema.