This review summarizes our findings concerning the altered balance of vasoactive systems (namely sympathetic nervous system and nitric oxide) in various forms of experimental hypertension – genetic hypertension (SHR, HTG rats), salt hypertension (Dahl rats) and NO-deficient hypertension (L-NAME-treated rats). An attempt is made to define relative NO deficiency (compared to the existing level of sympathetic vasoconstriction), to describe its possible causes and to evaluate particular indicators of its extent. A special attention is paid to reactive oxygen species, their interaction with NO metabolism, cell Ca2+ handling and blood pressure regulation. Our current effort is focused on the investigation of abnormal regulation of cytosolic Ca2+ levels in smooth muscle and endothelium of hypertensive animals. Such a research should cl
arify the mechanisms by which genetic and/or environmental factors could chronically modify blood pressure level.
This study investigated the contribution of reactive oxygen species (ROS) to blood pressure regulation in conscious adult male Wistar rats exposed to acute stress. Role of ROS was investigated in rats with temporally impaired principal blood pressure regulation systems using ganglionic blocker pentolinium (P, 5 mg/kg), angiotensin converting enzyme inhibitor captopril (C, 10 mg/kg), nitric oxide synthase inhibitor L-NAME (L, 30 mg/kg) and superoxide dismutase mimeticum tempol (T,25 mg/kg). Mean arterial pressure (MAP) was measured by
the carotid artery catheter and inhibitors were administered intravenously. MAP was disturbed by a 3-s air jet, which increased MAP by 35.2±3.0 % vs. basal MAP after the first exposure. Air jet increased MAP in captopril-
and tempol-treated rats similarly as observed in saline-treated rats. In pentolinium-treated rats stress significantly decreased MAP vs. pre
-stressvalue. In L-NAME-treated rats stress failed to affect MAP
significantly. Treatment of rats with P+L+C resulted in stress-induced MAP decrease by 17.3±1.3 % vs. pre-stress value and settling time (20.1±4.2 s). In P+L+C+T-treated rats stress led to maximal MAP decrease by 26.4±2.2 % (p<0.005 vs. P+L+C) and prolongation of settling time to 32.6±3.3 s (p<0.05 vs. P+L+C). Area under the MAP curve was significantly smaller in P+L+C-treated rats compared to P+L+C+T-treated ones (167±43 vs. 433±69 a.u., p<0.008). In conclusion, in rats with temporally impaired blood pressure regulation, the lack of ROS resulted in greater stress-induced MAP alterations and prolongation of time required to reach new post-stress steady state.
The insertion of mouse renin gene (Ren-2) into the genome of
normotensive rats causes a spontaneous rise of blood pressure
(BP), leading to an angiotensin II (Ang II)-dependent form of
hypertension in transgenic (mRen-2)27 rats (TGR). However,
enhanced sympathetic BP component was demonstrated in
heterozygous TGR aged 20 weeks. In the present study we used
another model, i.e. Cyp1a1-Ren-2 transgenic rats (iTGR) in which
hypertension can be induced by natural xenobiotic indole-3
carbinol (I3C) added to the diet. We investigated whether the
development of high blood pressure (BP) in 5-month-old iTGR
animals fed I3C diet for 10 days is solely due to enhanced
Ang II-dependent vasoconstriction or whether enhanced
sympathetic vasoconstriction also participates in BP maintenance
in this form of hypertension. Using acute sequential blockade of
renin-angiotensin system (RAS), sympathetic nervous system
(SNS) and NO synthase (NOS) we have demonstrated that the
observed gradual increase of BP in iTGR fed I3C diet was entirely
due to the augmentation of Ang II-dependent BP component
without significant changes of sympathetic BP component. Thus,
the hypertension in iTGR resembles to that of homozygous TGR
in which high BP was entirely dependent on Ang II-dependent
vasoconstriction. Moreover, our measurements of acute BP
response to Rho kinase inhibitor fasudil in animals subjected to
a combined blockade of RAS, SNS and NOS indicated the
attenuation of basal calcium sensitization in both iTGR and
homozygous TGR.