The participation of brain NO synthase in blood pressure control of adult spontaneously hypertensive rats

Abstract

Increased blood pressure (BP) in genetic hypertension is usually caused by high activity of sympathetic nervous system (SNS) which is enhanced by central angiotensin II but lowered by central nitric oxide (NO). We have therefore evaluated NO synthase (NOS) activity as well as neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS) protein expression in brainstem and midbrain of adult spontaneously hypertensive rats (SHR) characterized by enhanced sympathetic vasoconstriction. We also studied possible participation of brain NO in antihypertensive effects of chronic captopril treatment of adult SHR. NOS activity was increased in midbrain of SHR compared to Wistar-Kyoto (WKY) rats. This could be ascribed to enhanced iNOS expression, whereas nNOS expression was unchanged and eNOS expression was reduced in this brain region. In contrast, no significant changes of NOS activity were found in brainstem of SHR in which nNOS and iNOS expression was unchanged, but eNOS expression was increased. Chronic captopril administration lowered BP of adult SHR mainly by attenuation of sympathetic tone, whereas the reduction of angiotensin II-dependent vasoconstriction and the decrease of residual BP (amelioration of structural remodeling of resistance vessels) were less important. This treatment did not affect significantly either NOS activity or expression of any NOS isoform in the two brain regions. Our data do not support the hypothesis that altered brain NO formation contributes to sympathetic hyperactivity and high BP of adult SHR with established hypertension.

Multimodal Imaging in Rats Reveals Impaired Neurovascular Coupling in Sustained Hypertension

“…We found increased levels of eNOS in 20-week-old hypertensive animals; this may reflect a compensatory mechanism in response to reduced CBF, in accordance with earlier reports describing an upregulation of cerebral eNOS in SHRs. 47 A similar compensatory increase in eNOS has been described in rats on aging. Van der Loo et al 48 found an increase in O 2 − , trapping of vasorelaxant nitric oxide, and subsequent peroxynitrite formation, followed by nitration and inhibition of manganese superoxide dismutase.…”

Hemodynamic Characterization of Recombinant Inbred Strains: Twenty Years Later

“…Similarly, the NO system matched the BP effects of SNS very well in animals measured by radiotelemetry. This seems to be at variance with our earlier observations of a relative NO deficiency (lower NO-dependent vasodilatation compared to enhanced sympathetic vasoconstriction) in rats with genetic or salt hypertension (10,11,13). This discrepancy could be ascribed to strain differences, the greater age of the animals, or the absence of truly hypertensive rat strains in the present study.…”

“…The balance of major vasoactive systems was measured in conscious animals at the end of the experiment by consecutive inhibition of the reninangiotensin system (RAS), sympathetic nervous system (SNS), and nitric oxide synthase (NOS) (10,12,13).…”

Control of systemic and pulmonary blood pressure by nitric oxide formed through neuronal nitric oxide synthase

“…In anesthetized dogs, intracerebroventricular injection of ANG II was without effect on cardiac sympathetic afferent reflex, L-NAME alone augmented the reflex, and this excitatory effect was further increased in the presence of ANG II, and SMTC-induced augmentation of the reflex was abolished by pretreatment with losartan, suggesting that inhibition of nitric oxide is required for facilitation of the sympathetic afferent reflex by ANG II [104]. There was evidence showing that altered brain nitric oxide formation does not contribute to sympathetic hyperactivity and high blood pressure of adult SHR with established hypertension [105]. The role of brainstem nitric oxide in decreasing sympathetic nerve activity and systemic blood pressure is plausible in prehypertensive SHR.…”