Considering the finding that rats subjected to a hypobaric environment showed reduced NOS 27 , it may be possible that the hypoxia of the clipped kidneys could contribute to the attenuated up-regulation of nNOS, even though this experimental model is characterized by high levels of intrarenal Ang II 2.
Since NADPH oxidase activity can be stimulated by AT 1 receptors 28 , we also investigated the participation of oxidative stress in nNOS overexpression, and observed that treatment with tempol restored nNOS expression to basal levels in the non-clipped kidney. This finding indicated that, in addition to the role played by intracellular calcium 29 , superoxide anions could also participate in the intracellular mechanism of nNOS up-regulation.
Interestingly, nNOS expression in the clipped kidney was increased after the antioxidant treatment. A reasonable explanation for this result is based on previous studies 30,31 showing high levels of the anti-proteolytic agent hypoxia inducible factor HIF-1 under hypoxic conditions.
Since oxidative stress has deleterious effects on HIF-1 expression 32 , it is possible that, under clip-induced renal artery reduction of blood flow, the antioxidant tempol acted by preserving HIF-1 expression, consequently inhibiting tissue proteolysis and protecting against nNOS degradation. The anti-proteolytic effect of HIF-1 could also explain the smaller atrophy of the clipped kidney of tempol-treated 2K1C rats compared to the other 2K1C groups.
Cervenka et al. However, in the present study, we measured renal nNOS expression and observed that it was significantly increased in 2K1C hypertensive rats. To reconcile this obvious contradiction, we can assume that the enzyme activity, but not the protein level of nNOS, is decreased, as indirectly quantified by the cGMP method. These data could help explain why the hypertensive Ang II-infused rats did not present improvement of renal function in the study by these investigators In agreement with our results, Murakami et al.
In agreement with our results, there are indications that systemic oxidative stress is increased in renovascular hypertension 33,34 , which could lead to an enhanced release of superoxide anions O 2 - , mainly due to Ang II 28, Moreover, others have shown that nNOS can generate superoxide anions, mainly under situations of depletion of substrates or co-factors 35 , also contributing to O 2 - production and impaired NO bioavailability. The reason 2K1C animals treated with low doses of losartan or tempol showed a marked reduction of cGMP levels may have been that they were still Ang II-dependent hypertensive when compared with sham animals.
In addition, the low or undetectable levels of cGMP mainly in the non-clipped kidney of 2K1C-losartan and 2K1C-tempol rats was expected because the levels of the second messenger follow the expression of nNOS, which was restored in these two groups when compared with the 2K1C group. Although in the present study we did not measure the expression of eNOS, its participation should be considered.
The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev ; Unraveling the mystery of Goldblatt hypertension. News Physiol Sci ; Nitric oxide-angiotensin II interactions in angiotensin II-dependent hypertension.
Acta Physiol Scand ; Effects of NG-nitro-L-arginine on pressure natriuresis in anaesthetized rabbits. Clin Exp Pharmacol Physiol ; Nitric oxide in the control of renal hemodynamics and excretory function. Am J Hypertens ; 74SS. Differential renal response to Nomega-nitro-L-arginine methyl ester and L-arginine in rats with hypertensive or diabetic nephropathy. J Cardiovasc Pharmacol ; Role of nitric oxide in regional blood flow in angiotensin II-induced hypertensive rats.
Hypertens Res ; Influence of nitric oxide derived from neuronal nitric oxide synthase on glomerular filtration. Gen Pharmacol ; Kone BC, Baylis C. Biosynthesis and homeostatic roles of nitric oxide in the normal kidney. Am J Physiol ; FF Increased blood pressure in rats after long-term inhibition of the neuronal isoform of nitric oxide synthase. J Clin Invest ; Role of macula densa neuronal nitric oxide synthase in renal diseases.
Med Mol Morphol ; Nitric oxide synthase I immunoreactivity in the macula densa of the kidney is angiotensin II dependent. Kidney Int Suppl ; SS Role of nNOS in regulation of renal function in hypertensive Ren-2 transgenic rats.
Improved Hypertension Control After Disclosure of Decades-Old Trauma
Physiol Res ; Diminished expression of constitutive nitric oxide synthases in the kidney of spontaneously hypertensive rat. Clin Exp Hypertens ; Role of angiotensin II and free radicals in blood pressure regulation in a rat model of renal hypertension. Hypertension ; Here, we identified our most important clinical finding. We used microneurography and a complex autonomic blockade protocol to show that affected subjects were incapable of performing baro-reflex blood pressure not heart rate buffering. Meanwhile, we sought to narrow down the gene locus on chromosome 12p. We came upon a publication from Japanese investigators describing a deletion syndrome that involved a portion of our linkage interval; the affected child had brachydactyly.
The investigators graciously provided us with DNA that allowed us to map the deletion precisely. This endeavor decreased the size of our interval by half. We also identified other families and were helped generously by colleagues. Our attention was drawn to SOX-5, a transcription factor involved in collagen I deposition in fingers and elsewhere.
The gene lies adjacent to our interval, but single nucleotide polymorphisms served to eliminate the gene for further direct consideration.
Our clinical attention was drawn to possible central mechanisms causing the hypertension related to neurovascular contact at the rostral ventrolateral medulla. This finding led to another CRC investigation of baroreceptor reflex function in the family. We found that a major defect in baroreceptor reflex blood pressure buffering was present, similar to that observed in patients with primary autonomic failure. The neurovascular contact could be eliminated operatively.
However, a molecular understanding is necessary before taking such a step. With interphase fluorescence in-situ hybridization FISH , we were able to show that a chromosomal rearrangement had occurred at the 12p locus.
This finding raised the order of complexity substantially. Again, the mechanisms remained elusive. We next performed a 26 bacterial artificial chromosome BAC array to define the rearrangement further. They were all different, although a common pattern was apparent. No known genes lie within this interval; however, three expressed sequence tags EST map to it. This finding raises the possibility that the gene s involved does not code for protein.
Indeed, the structures we have produced raise the hypothesis that we are dealing with a regulatory form of RNA called micro or miRNA. The rearrangement must be verified with other techniques such as fiber FISH or chromosome orientation FISH, since our attempts at defining break points with Southern blotting have been unsuccessful. We are aware that newer technical developments including cytoband capture, enrichment, and subsequent next generation sequencing techniques may help us further.
The affected patients are all under effective treatment, and no adverse cardiovascular events have as yet occurred. We continue to believe that elucidation of this syndrome will be of relevance to essential hypertension. A linkage analysis in Chinese patients with essential hypertension but without short fingers supports this view.
Finally, we have become students of brachydactyly; there are many kinds. Our patients have type E brachydactyly that features cone-shaped epiphyses Figure. Most persons with brachydactyly do not have hypertension.
Now is the Time to Tackle Hypertension in Haiti
Your Pumping Station Your heart and arteries have a big impact on blood pressure. The amount of blood your heart pumps, how wide or narrow your arteries are, and the volume of blood in your bloodstream all affect your blood pressure. If your arteries are too narrow, if you have greater-than-normal blood volume, or if your heart beats more forcefully than it should, high blood pressure can occur.
The question is, what causes these things to happen?
- Adrenal tumours linked to high blood pressure.
- Opal: The Journal of an Understanding Heart?
- Land of Eagles?
- Twice as many children now have high blood pressure than they did a decade ago | Daily Mail Online.
- Starting and Operating a Business in New Hampshire (Starting and Operating a Business in the U.S. Book 2016).
It's not always clear. Get the full picture of how the heart functions. Your Nerves Your autonomic nervous system is a key blood pressure player. It helps regulate your blood pressure by setting off a series of events in response to low or high blood pressure.
The progress notes of Michel Accad, MD
When your blood pressure dips too low -- or when your body needs to prime itself to take sudden action against a perceived threat, such as during times of stress or fear -- the sympathetic part of the autonomic nervous system temporarily raises blood pressure. It does this by influencing chemical messengers that affect the speed and force of your heartbeat and the size of your blood vessels. When your blood pressure is too high, or when it's time for sleep or rest, the parasympathetic part of the autonomic nervous system kicks in, conserving energy and releasing acetylcholine, a neurotransmitter that slows down your heart.
It's not clear if dysfunction of the autonomic nervous system may contribute to hypertension in some way. Recent research does show that the sympathetic nervous system may be overactive in some people with hypertension. Your Beans Your kidneys -- those bean-shaped organs that flank your spine -- also play a pivotal role in keeping blood pressure in a healthy range.