Changes in central and peripheral renin-angiotensin system after furosemide injection

To examine the effects of acute stimulation on the peripheral and central renin-angiotensin system, simultaneous sampling of blood and cerebrospinal fluid (CSF) for measurements of plasma renin activity (PRA), plasma angiotensin I-immunoreactivity (PAng I-ir), plasma angiotensin II-immunoreactivity (PAng II-ir), plasma angiotensinogen and cerebrospinal fluid angiotensin II-ir (CSF Ang II-ir) and CSF angiotensinogen was carried out following intravenous injection of furosemide (5 mg/kg) in conscious dogs. Administration of furosemide induced marked increases in PRA, Ang I-ir, PAng II-ir and CSF Ang II-ir, however, neither plasma nor CSF angiotensinogen was changed. Furthermore, a relatively large dose (20 mg/kg/min) of intravenously infused synthetic Ang II for 20 min produced a five-fold increase in PAng II-ir compared with no significant increase in CSF Ang II-ir. In spite of significant suppression of PRA and PAng I-ir, there were no significant changes in either plasma or CSF angiotensinogen. These results primarily suggest that the peripheral and the brain renin-angiotensin systems may be linked and that acute changes in the peripheral renin-angiotensin system do not alter either plasma or CSF angiotensinogen.     

Antihypertensive effects of I-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine on plasma renin activity and catecholamine responses in spontaneously hypertensive rats

Fourteen 23 week old male spontaneously hypertensive rats (SHR) were randomly divided into saline control or phospholipid (I-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine) treatment groups. Four weeks of baseline systolic blood pressure (SBP) and heart rate (HR) measurements were determined via tail plethysmography. On week 25 of the baseline period a 1.5 ml blood sample was taken by tail clip for analysis of norepinephrine (NE), epinephrine (E), and plasma renin activity (PRA). On the following week, a single injection of phospholipid (11 ug/kg, s.c.) was given to the experimental animals following baseline SBP and HR determinations. A similar procedure was employed for control subjects, except they received an injection of normal saline (0.5 ml, s.c.). Systolic BP and HR responses were monitored for 24 minutes following the injection. A 1.5 ml blood sample was taken at the end of the 4th minute for NE, E, and PRA assays. A significant drop in SBP (202 +/- 5 mmHg to 124 +/- 6 mmHg) and an increase in HR (431 +/- 17 bpm to 519 +/- 21 bpm) were observed for experimental animals, but not for control subjects. Plasma NE increased significantly (446 +/- 42 pg/ml to 1099 +/- 77 pg/ml), but E remained unchanged following treatment with the phospholipid. Plasma renin activity increased for both groups, but this change was only significant for the experimental group (18.1 +/- 5.7 ng Al/ml/hr to 34.3 +/- 3.6 ng Al/ml/hr). Thus, it appears that I-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine is a potent antihypertensive vasodilating agent which stimulates baroreceptor mediated sympathetic discharge to the heart and kidneys of the SHR.     

Vascular renin-like activity in aorta and mesenteric artery of the rat

Vascular renin-like enzymatic activity (VRLA) has been measured in the artery wall of control and experimental rats. The following groups have been studied: 1-normal salt diet; 2-high salt diet; 3-low salt diet; 4-bilateral nephrectomy (Nx); 5-sham operated for Nx. VRLA was evaluated in the aorta (ARLA) and in the mesenteric arteries (MRLA). Blood samples were obtained for plasma renin activity (PRA) determination. High salt diet decreased PRA, ARLA and MRLA whereas low salt diet increased PRA, did not change ARLA and decreased MRLA. PRA was almost undetectable in Nx animals while ARLA showed a 40% reduction and MRLA was unchanged in these animals. These results would indicate that the changes in PRA induced different variations in the renin-like content of the aorta and the mesenteric artery. The differences could be mainly due to two factors: 1) the capacity of the vascular tissue to bind circulating renin and 2) the capacity of each tissue to synthetize renin-like material in situ.     

Action of 3-beta adrenolytics on plasma renin activity measured by radioimmunology in genetically hypertensive rats]

Spontaneously hypertensive rats (SHR) have basal levels of plasma renin activity (PRA) lower than the ones observed in normal Sprague Dawley rats. Three beta blocking agents are orally administered to unanesthetized spontaneously hypertensive and normotensive rats. Propranolol and S 464 reduce PRA in spontaneously hypertensive and normotensive control rats. Pindolol do not lower PRA in normotensive rats but increases levels of PRA in spontaneously hypertensive rats. These results are discussed.     

Chloride channel activity of vascular smooth muscle in the spontaneous hypertensive rats

To characterize the activity of the Ca2+-activated Cl- channels in vascular smooth muscle (VSM) of the spontaneous hypertensive rats (SHR), the isolated mesenteric vascular beds and tail artery strips were preparated from SHR and Wistar rats aged 7-8 weeks. The changes in contractile response to norepinphrine (NE) were taken as an index of vascular mortion. Results showed that the contractile responses of mesenteric arteries and tail arteries to NE in SHR were significantly greater than that in Wistar rats. The inhibition magnitude of the contractile response by Ca2+-activated Cl- channel blocker, niflumic acid in SHR was significantly less than that in Wistar rats. Decreasing the extracellular Cl- concentration increased the contractile response to NE significantly, but the amplitude of enhanced contractile response in SHR was greater than that in Wistar rats. It can be concluded that NE-induced contraction was enhanced in SHR, which is partly due to an increase in Cl- efflux through the Ca2+-activated Cl- channels. The chloride channel activity may be increased in association with the elevation of blood pressure.     

Increased brain uptake and brain to blood efflux transport of 14C-GABA in spontaneously hypertensive rats

The brain uptake and brain to blood efflux transport of (14)C-GABA were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats using 20 min bilateral in situ brain perfusion in rats anesthetized using urethane. The volume of distribution (Vd) of (14)C-GABA into cerebrospinal fluid (CSF) and brain regions (cortex, diencephalon, cerebellum, and brain stem) was significantly greater in SHR than in the corresponding regions in WKY rats (p<0.05). The estimated Vd value of (14)C-GABA in CSF of SHR was 3.4 fold greater than that in WKY. Also compared to WKY, the Vd of (14)C-GABA into cerebellum and cortex of SHR was 15.3 fold and 19.4 fold greater, respectively. Although the study of blood-brain barrier (BBB) integrity using (3)H-mannitol revealed increased paracellular permeability at the brain capillaries of SHR when compared to WKY rats, this was found to be only partially responsible for the increased (14)C-GABA uptake. The study of brain to blood efflux transport of (14)C-GABA (after loading of brain with (14)C-GABA by vascular perfusion) revealed that the half-time of elimination was significantly shorter in SHR (5.35+/-0.66 min) than in WKY rats (14.83+/-1.94 min), (p<0.001). HPLC analysis revealed that GABA concentrations in brain extracts and CSF of SHR were similar to those in WKY rats (p>0.05). The faster efflux in SHR might be, at least partially, responsible to compensate for increased uptake of this neurotransmitter and to preserve the protective function of BBB towards GABA. The protective function of the BCSFB towards GABA appears to be also preserved, since systemic infusion of GABA within a wide range of administered doses (0.004-5.00 mg/kg) produced an increase in GABA CSF concentration from around 0.5 microM to only 11 microM, and the obtained pattern of CSF GABA concentrations under these conditions did not differ between SHR and WKY rats, as revealed by HPLC.     

Renal Na+-K+-ATPase in weanling and adult spontaneously hypertensive rats

The interrelationships among plasma renin activity (PRA, ng AI/ml plasma/hr), aldosterone concentration (ng%), and renal Na+-K+-ATPase activity (mumole PO4/mg protein/hr) were studied in 9 weanling normotensive spontaneously hypertensive rats (SHR), 9 adult hypertensive SHR, and 9 weanling and 9 adult normotensive Wistar-Kyoto rats (WKY). All groups were placed on a normal (0.4% sodium) diet. PRA and plasma aldosterone, measured in samples drawn from the ether-anesthetized rat, were higher in weanling SHR (15.2 +/- 2.0, 37 +/- 4.2) than in WKY. PRA measured in samples collected from a separate group of unanesthetized weanling SHR was also greater than in age-matched WKY. In adult SHR, PRA (6.1 +/- 0.9) and plasma aldosterone (20.0 +/- 2.7) were decreased. During the weanling period Na+-K+-ATPase activity in SHR was not only greater than in age-matched WKY but was also increased compared to adult normotensive and hypertensive rats (137 +/- 9 weanling SHR, 89 +/- 7 weanling WKY, 73 +/- 11 adult SHR, 84 +/- 17 adult WKY). Thus, during the weanling period the renin-angiotensin-aldosterone (R-A-A) system and renal Na+-K+-ATPase activity are activated in SHR. The elevation of Na+-K+-ATPase activity may be due to increased aldosterone levels. It was noted, however, that plasma aldosterone was similar in adult WKY and weanling SHR, while Na+-K+-ATPase activity was higher in SHR. These findings involving R-A-A and renal Na+-K+-ATPase activity prior to the elevation of blood pressure suggest that the kidneys may play a role in the initiation of hypertension in SHR.     

Effects of ethanol on brain monoamine content of spontaneously hypertensive rats (SHR)

Spontaneously hypertensive rats (SHR) were administered either 2.4 g/kg ethanol or an isocaloric glucose daily for 4 weeks and the levels of norepinephrine (NE), epinephrine (EP), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in different brain regions were determined. Results indicated a 3-fold increase in NE level in brain stem and hypothalamus and more than 2-fold increase in DA in corpus striatum in alcohol-treated rats as compared to controls. There was a significant increase in the level of DA in the corpus striatum but the levels in cerebral cortex, brain stem and hippocampus were decreased instead. Decreases in 5-HT levels were found in hypothalamus, brain stem, cortex and cerebellum of alcohol-treated brain as compared to untreated controls. These results indicate alterations of the biogenic amine contents in different regions of the SHR brain after chronic ethanol ingestion. Since stimulated release of biogenic amines in the SHR brain has been implicated in the regulation of blood pressure, changes due to ethanol ingestion may be a risk factor in hypertensive patients.     

Vascular and brain neuropeptide Y in banded and spontaneously hypertensive rats

Debate exists regarding the relative importance of neuropeptide Y (NPY) in the pathogenesis of genetic and non-genetic hypertension. NPY concentrations were compared in conduit, mesenteric and renal vasculatures and in hypothalamic and medullary regions of age-matched normotensive control, aortic banded and spontaneously hypertensive rats (SHRs). Lower NPY concentrations were measured in the pre-optic area of banded rats compared to controls and SHR. Renal vein NPY levels were reduced in banded animals, whereas renal artery levels were decreased in SHR. In mesenteric arteries, NPY concentration was selectively increased in SHR. These findings suggest that local hemodynamic alterations influence endogenous levels of this potent vasoconstrictor.     

Release of prostaglandins by the mesenteric artery of the renovascular and spontaneously hypertensive rat

The release of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin (PGI2), by the perfused mesenteric arteries of renal and spontaneously hypertensive rats (SHR) have been measured. Unstimulated mesenteric arteries from two-kidney one-clip hypertensive rats (2K-1C) released 1.6 times as much PGE2 and 2.7 times as much 6-keto-PGF1 alpha as those of control rats. The release of PGE2 by mesenteric arteries from one-kidney one-clip hypertensive rats (1K-1C) was not significantly different from that of uninephrectomized normotensive rats, but the release of 6-keto-PGF1 alpha was 3.5 times higher in the former than in the latter. Norepinephrine (NE) induced a dose-related increase in perfusion pressure, in PGE2, and 6-keto-PGF1 alpha release in all four groups. However, its effect on the release of PGE2 was more pronounced in 2K-1C than in sham-operated rats. There was no difference between 1K-1C and the uninephrectomized group. The effect of NE on the release of 6-keto-PGF1 alpha was significantly higher for both renal hypertensive groups. These results indicate that the release of PGE2 is more dependent on the loss of renal mass than on hypertension, while the reverse applies to the release of 6-keto-PGF1 alpha. Unstimulated mesenteric arteries from SHR released less PGE2 and less 6-keto-PGF1 alpha than those of Wistar-Kyoto normotensive rats (WKY), but the release was not significantly different from Wistar rats. Under NE stimulation, WKY mesenteric arteries showed almost no increase in release of PGs. Compared with those of Wistar rats, SHR mesenteric arteries showed a greater pressor response to NE, a lower PGE2 release, and the same release of 6-keto-PGF1 alpha. These findings reveal the difficulty of selecting an appropriate control group in studies involving SHR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats

Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) synthesize type 1 nitric oxide synthase (NOS1) and type 2 cyclooxygenase (COX-2). Both nitric oxide (NO) and prostaglandins have been considered to mediate or modulate the control of renin secretion. Reactive oxygen species (ROS) produced locally by NADPH oxidase may influence NO bioavailability. We have tested the hypothesis that in hypertension elevated ROS levels may modify the expression of NOS1 and COX-2 in the JGA, thereby interacting with juxtaglomerular signaling. To this end, spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats (WKY) received the specific NADPH oxidase inhibitor, apocynin, during 3 wk. Renal functional and histochemical parameters, plasma renin activity (PRA), and as a measure of ROS activity, urinary isoprostane excretion (IP) were evaluated. Compared with WKY, IP levels in untreated SHR were 2.2-fold increased, and NOS1 immunoreactiviy (IR) of JGA 1.5-fold increased, whereas COX-2 IR was reduced to 35%, renin IR to 51%, and PRA to 7%. Apocynin treatment reduced IP levels in SHR to 52%, NOS1 IR to 69%, and renin IR to 62% of untreated SHR, whereas renin mRNA, COX-2 IR, glomerular filtration rate, PRA, and systolic blood pressure remained unchanged. WKY revealed no changes under apocynin treatment. These data show that NADPH oxidase is an important contributor to elevated levels of ROS in hypertension. Upregulation of MD NOS1 in SHR may have the potential of blunting the functional impact of ROS at the level of bioavailable NO. Downregulated COX-2 and renin levels in SHR are apparently unrelated to oxidative stress, since apocynin treatment had no effect on these parameters.     

Angiotensin biosynthesis and concentrations in brain of normotensive and hypertensive rats

We report here on the extraction and characterization of angiotensin I (ANG I) and angiotensin II (ANG II) from the brain of rats. High pressure liquid chromatography (HPLC) with different mobile phases combined with specific radioimmunoassays (RIA) proved to be a powerful tool for peptide characterization in biological samples; (Ile5)-ANG I, (Ile5)-ANG II and (Ile5)-ANG III could clearly be identified in cerebrospinal fluid (CSF), incubated in vivo and in vitro with renin, in total brain extracts, as well as in hypothalamus (HT), medulla oblongata (MO), cerebellum (CER) and cortex (CO). Angiotensin cleaved from CSF angiotensinogen and angiotensin extracted from brain showed retention times identical to those of plasma angiotensin and synthetic standard peptides, indicating that their amino acid sequence is probably identical. ANG I and ANG II were highest in the HT and lowest in the CO. Following bilateral nephrectomy (NX) both ANG I and ANG II persisted at control levels. Young 10 week old spontaneously hypertensive rats (SHRSP) showed significantly lower ANG I and ANG II concentrations in the HT compared with Wistar Kyoto rats (WKY). Intracerebroventricular (i.c.v.) administration of the converting enzyme inhibitor captopril caused a significant increase in ANG 1 in nephrectomized SHRSP but not in WKY. These differences were not found in 40 week old SHRSP. The data show that ANG I and ANG II are synthetized in the brain of rats. The lower concentrations and the enhanced accumulation of ANG I after converting enzyme blockade in nephrectomized young SHRSP indicate an increased turnover of angiotensin in hypertensive rats.     

Cyclic nucleotide levels in brains of control and hypertensive rats.

Adenosine 3′, 5′-monophosphate (cyclic AMP) and guanosine 3′,5- monophosphate (cyclic GMP) levels were measured in seven brain areas of spontaneously hypertensive rats (SHR) and two groups of control rats. In cerebral cortex, hypothalamus, pons-medulla oblongata and cerebellum cyclic AMP levels were higher in SHR than in Wistar-Kyoto controls. Cyclic GMP levels were higher in SHR than in Wistar-Kyoto rats in all brain areas except for the striatum and hippocampus where the levels were lower. There were also some differences in cyclic nucleotide levels between Wistar-Kyoto and Wistar-Charles River controls.     

The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment

Recent clinical and animal studies have shown that collateral artery growth is impaired in the presence of vascular risk factors, including hypertension. Available evidence suggests that angiotensin-converting enzyme inhibitors (ACEI) promote collateral growth in both hypertensive humans and animals; however, the specific mechanisms are not established. This study evaluated the hypothesis that collateral growth impairment in hypertension is mediated by excess superoxide produced by NAD(P)H oxidase in response to stimulation of the ANG II type 1 receptor. After ileal artery ligation, mesenteric collateral growth did not occur in untreated, young, spontaneously hypertensive rats. Significant luminal expansion occurred in collaterals of spontaneously hypertensive rats treated with the superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and the ACEI captopril, but not ANG II type 1 (losartan) or type 2 (PD-123319) receptor blockers. The ACEI enalapril produced equivalent reduction of arterial pressure as captopril but did not promote luminal expansion. This suggests the effects of captopril on collateral growth might result from its antioxidant properties. RT-PCR demonstrated that ANG II type 1 receptor and angiotensinogen expression was reduced in collaterals of untreated rats. This local suppression of the renin angiotensin system provides a potential explanation for the lack of effect of enalapril and losartan on collateral growth. The results demonstrate the capability of antioxidant therapies, including captopril, to reverse impaired collateral artery growth and the novel finding that components of the local renin angiotensin system are naturally suppressed in collaterals.     

Effects of acute exercise and prolonged exercise training on blood pressure, vasopressin and plasma renin activity in spontaneously hypertensive rats

The purpose of this study was to investigate the effect of swimming training on systolic blood pressure (BPs), plasma and brain vasopressin (AVP), and plasma renin activity (PRA) in spontaneously hypertensive rats (SHR) during rest and after exercise. Resting and postexercise heart rate, as well as blood parameters such as packed cell volume (PCV), haemoglobin concentration (Hb), plasma sodium and potassium concentrations ([Na+], [K+]) osmolality and proteins were also studied. Hypophyseal AVP had reduced significantly after exercise in the SHR, whereas PRA had increased significantly in the Wistar-Kyoto (WKY) strain used as normotensive controls. Plasma AVP concentration increased in both strains. By the end of the experiment, training had reduced body mass and BPs by only 10% and 6%, respectively. Maximal oxygen uptake was increased 10% and plasma osmolality 2% by training. The postexercise elevation of heart rate was not significantly attenuated by training. A statistically significant reduction in postexercise plasma osmolality (10%) and [Na+] (4%) was observed. These results suggested that swimming training reduced BPs. Plasma and brain AVP played a small role in the hypertensive process of SHR in basal conditions because changes in AVP contents did not correlate with those of BPs. Moreover, there were no differences between SHR and WKY in plasma, hypophyseal and hypothalamic AVP content in these basal conditions. Finally, during moderate exercise a haemodilution probably occurred with an increase of plasma protein content. This was confirmed by the exercise-induced increase of plasma AVP and the reduction of hypophyseal AVP content, suggesting a release of this hormone, which probably contributed to the water retention and haemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)     

High Salt Intake Damages the Heart through Activation of Cardiac (Pro) Renin Receptors Even at an Early Stage of Hypertension

Objective

It has not yet been fully elucidated whether cardiac tissue levels of prorenin, renin and (P)RR are activated in hypertension with a high salt intake. We hypothesized that a high salt intake activates the cardiac tissue renin angiotensin system and prorenin-(pro)renin receptor system, and damages the heart at an early stage of hypertension.

Methods

Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) received regular (normal-salt diet, 0.9%) and high-salt (8.9%) chow for 6 weeks from 6 to 12 weeks of age. The systolic blood pressure, plasma renin activity (PRA) and plasma angiotensin II concentration were measured, and the protein expressions of prorenin, (pro)renin receptor, angiotensinogen, angiotensin II AT1 receptor, ERK1/2, TGF-β, p38MAPK and HSP27 in the myocardium were investigated. The cardiac function was assessed by echocardiography, and histological analysis of the myocardium was performed.

Results

The high-salt diet significantly increased the systolic blood pressure, and significantly reduced the PRA and plasma angiotensin II concentration both in the WKYs and SHRs. Cardiac expressions of prorenin, renin, (P)RR, angiotensinogen, angiotensin II AT1 receptor, phosphorylated (p)-ERK1/2, p-p38MAPK, TGF-β and p-HSP27 were significantly increased by the high salt diet both in the WKYs and SHRs. The high-salt diet significantly increased the interventricular septum thickness and cardiomyocyte size, and accelerated cardiac interstitial and perivascular fibrosis both in the WKYs and SHRs. On the other hand, dilatation of left ventricular end-diastolic dimension and impairment of left ventricular fractional shortening was shown only in salt loaded SHRs.

Conclusion

The high-salt diet markedly accelerated cardiac damage through the stimulation of cardiac (P)RR and angiotensin II AT1 receptor by increasing tissue prorenin, renin and angiotensinogen and the activation of ERK1/2, TGF-β, p38MAPK and HSP27 under higher blood pressure.     

Intracellular renin increases the inward calcium current in smooth muscle cells of mesenteric artery of SHR. Implications for hypertension and vascular remodeling

The influence of intracellular renin on the inward calcium current in isolated smooth muscle cells from SHR mesenteric arteries was investigated. Measurements of calcium current were performed using the whole cell configuration of pCLAMP. The results indicated that: 1) renin (100 nM) dialyzed into smooth muscle cells, increased the inward calcium current; 2) verapamil (10–9 M) administered to the bath inhibited the effect of renin on the inward calcium current; 3) concurrently with the increase of calcium current a depolarization of 6.8 +/− 2.1 mV (n = 16)(P < 0.05) was found in cells dialyzed with renin; 4) intracellular dialysis of renin (100 nM) into smooth muscle cells isolated from mesenteric arteries of normal Wystar Kyoto rats showed no significant change on calcium current; 5) aliskiren (10–9 M) dialyzed into the cell together with renin (100 nM) abolished the effect of the enzyme on the calcium current in SHR; 6) Ang II (100 nM) dialyzed into the smooth muscle cell from mesenteric artery of SHR in absence of renin, decreased the calcium current-an effect greatly reduced by valsartan (10–9 M) added to the cytosol; 7) administration of renin (100 nM) plus angiotensinogen (100 nM) into the cytosol of muscles cells from SHR rats reduced the inward calcium current; 8) extracellular administration of Ang II (100 nM) increased the inward calcium current in mesenteric arteries of SHR. Conclusions: intracellular renin in vascular resistance vessels from SHR due to internalization or expression, contributes to the regulation of vascular tone and control of peripheral resistance-an effect independently of Ang II. Implications for hypertension and vascular remodeling are discussed.     

Increased sympathetic innervation in the cerebral and mesenteric arteries of hypertensive rats

The density of catecholamine-containing nerve fibers was studied in the cerebral and mesenteric arteries from normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP) in the growing (SHR, WKY) and adult (SHR, SHRSP, WKY) animals. Cerebral arteries from SHR showed an increased adrenergic innervation from day 1. The nerve plexuses reached an adult pattern earlier in SHR than in WKY. The arteries from adult SHR and SHRSP (22 weeks old) showed a markedly higher nerve density than WKY. There was a positive linear correlation between blood pressure and nerve density for four cerebral arteries. The mesenteric arteries were not innervated at birth. However, hyperinnervation of these arteries in the SHR was already present at 10 days of age as compared with WKY. Sympathectomy with anti-nerve growth factor and guanethidine caused a complete disappearance of fluorescent fibers in the mesenteric arteries from SHR and WKY, and in the cerebral arteries of WKY. The same procedure caused only partial denervation of the cerebral arteries from hypertensive animals. We postulate that the increase in nerve density in the cerebral arteries from the hypertensive rats may contribute to the development of arterial hypertrophy in chronic hypertension through the trophic effect of the sympathetic innervation on vascular structure.     

Prostaglandins and thromboxane outflow from the perfused mesenteric vascular bed in spontaneously hypertensive rats

To clarify the metabolism of PGE2, prostacyclin (PGI2) and thromboxane A2 (TxA2) in small vessels in spontaneously hypertensive rats (SHR), we removed superior mesenteric vascular beds from 10 week old SHR and age matched normotensive controls (WKY). The mesenteric artery was perfused with Krebs-Henseleit buffer and samples of effluent collected every 15 minutes during 3 hours perfusion for analysis of PGE2, 6-keto-PGF1 alpha (a stable metabolite of PGI2) and TxB2 (a stable metabolite of TxA2) by specific radioimmunoassays. Levels of all three arachidonic acid (AA) metabolites, PGE2, 6-keto-PGF1 alpha and TxB2, in the mesenteric effluent were significantly reduced in SHR as compared to WKY. TxB2 was detected in all samples throughout the perfusion. 6-keto-PGF1 alpha/PGE2 ratios and TxB2/PGE2 ratios were significantly increased in SHR. 6-keto-PGF1 alpha/TxB2 ratios in the first four samples were significantly decreased in SHR as compared to WKY. These data suggest that there may be reduced availability of PG precusor AA and unbalanced synthesis of PGs in small vessels in SHR. Both may have relevance to the development of hypertension in the animals.