Decreased Na+ K +ATPase Activity in the Aortic Endothelium and Smooth Muscle of the Spontaneously Hypertensive Rats

The activity of Na⁺ K⁺ ATPase in the endothelium and smooth muscle of the aortae of normotensive and hypertensive rats was investigated. The enzyme activity in the endothelium and smooth muscle of the spontaneously hypertensive rats (SHR) was 2.15 ± 0.48 and 12.98±0.99 respectively. These values were significantly lower (P<0.05) than the enzyme activity in the corresponding tissues (10.10 ± 1.78 for endothelium, 20.77 ± 2.54 for smooth muscle) of the normotensive Wistar Kyoto (WKY) rats. However, with the low blood pressure spontaneously hypertensive rats (LBP-SHR) i.e. in those animals whose blood pressures were below 150 mm Hg, the enzyme activity in both tissues was not significantly different from those of the WKY. Since Na⁺ K⁺ ATPase is coupled to the sodium-potassium pump whose activity affects the functions of other pumps, the results indicate that the development of high blood pressure in the SHR may be related to an alteration in the transport of cations across the cell membrane.     

Relationship Between Exercise Heart Rate Recovery and Circadian Blood Pressure Pattern

J Clin Hypertens (Greenwich). 2010;12:407–413. ^©2010 Wiley Periodicals, Inc. The aim of the present cross-sectional study was to evaluate heart rate recovery (HRR) in normotensive and hypertensive individuals with either nondipper or dipper type circadian rhythm of blood pressure. Eighty-five patients were divided into 4 groups according to the presence of hypertension and pattern of circadian blood pressure as follows: (1) normotensive/dipper, n=20; (2) normotensive/nondipper, n=21; (3) hypertensive/dipper, n=22; and (4) hypertensive/nondipper, n=22. HRR indices were calculated by subtracting first, second, and third minute heart rates from the maximal heart rate obtained during stress testing and designated as HRR1, HRR2, and HRR3. Mean HRR1 values (29.7±4.0 vs 26.6±3.7, P=.016) were significantly higher in the normotensive/dipper group than the normotensive/nondipper group. Mean HRR1 values (28.6±4.0 vs 24.8±4.6 beats per minute, P=.007) were higher in the hypertensive/dipper group than the hypertensive/nondipper group. Spearman’s correlation analyses revealed a positive correlation between degree of nighttime dipping and HRR1 (r=.600, P=.001). The correlation coefficient between degree of nighttime dipping and HRR1 was higher in the hypertensive group than the normotensive group (r=.676, P=.001 and r=.575, P=.001, respectively). Blunting of the nocturnal fall in blood pressure associates with a delayed recovery of heart rate after graded maximal exercise in both normotensive and hypertensive groups.     

Erythrocyte Membrane Abnormalities in Hypertension: A Comparison Between two Animal Models

Calcium-membrane interactions have been studied in two animal models of hypertension using the erythrocyte membrane as a model system. The Okamoto-Aoki strain of spontaneously hypertensive rats (SHR) was the first examined, and the activities of the Ca⁺⁺/Mg⁺⁺-ATPases in the membrane of SHR erythrocytes were found to be consistently higher than those of the normotensive controls (WKY), while other membrane enzymes such as Na⁺/K⁺-ATPase and acetylcholinesterase were not detectably altered. Erythrocyte membranes of the SHR also have a higher passive permeability to calcium as well as other functional and compositional differences when compared to those of the WKY. These findings suggest that the membrane alterations in the SHR may be related to an increased passive permeability to calcium, and a possibly compensatory increase in Ca⁺⁺/Mg⁺⁺-ATPase activity in these animals. The second animal model examined was the deoxycorticosterone/salt-induced hypertension (DOCA) in uni-nephrectomized rats. In DOCA rats with comparable degree of blood pressure elevation, none of the erythrocyte membrane abnormalities observed in the SHR were present, suggesting that the latter alterations are probably genetically determined and not a consequence of elevated arterial pressure.     

Influence of spontaneous hypertension and cardiac hypertrophy on the severity of ischemic arrhythmias in the rat

Summary Cardiac hypertrophy (CH) and hypertension (HT) are major determinants of sudden cardiac death in patients with coronary artery disease. To investigate the hypothesis that CH and HT increase the incidence of severe ventricular arrhythmias in an animal model, we performed a 30-min period of coronary artery ligation in anesthetized spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto (WKY) and Wistar (W) rats. The incidence and duration of ventricular fibrillation resulting from coronary artery occlusion were significantly (p<0.01) increased in hypertensive rats compared to normotensive animals. The calcium entry blocker nicardipine was administered orally to SHR either chronically for 8 weeks (20 mg·kg^–1 twice daily) or acutely as a single dose of 20 mg·kg^–1. After long-term treatment with nicardipine, left ventricular hypertrophy index and systolic blood pressure were significantly (p<0.001) reduced when compared to vehicle-treated SHR, whereas a single administration of nicardipine only decreased blood pressure without affecting cardiac mass. In the long-term nicardipine-treated SHR group, acute coronary artery ligation induced significantly less ventricular fibrillation (p<0.05) and mortality (p<0.001) than in acutely nicardipine-treated or untreated SHR groups. In conclusion, the data suggest that the severity and incidence of lethal ventricular arrhythmias are more elevated in hypertensive than in normotensive rats and this may be related to the myocardial hypertrophic state.     

Hypotensive responses to centrally administered taurine in DOCA-salt hypertensive and spontaneously hypertensive rats

The present study was designed to investigate the short-term effects of intracerebroventricularly-administered taurine in DOCA-salt hypertensive (DOCA), spontaneously hypertensive (SHR) and their respective normotensive control rats anesthetized with urethane. Blood pressure, heart rate and sympathetic nerve activity were consistently decreased following the injection of taurine 150 micrograms per rat in hypertensive rats as well as in normotensive controls of the two groups. Percent changes from the baselines in blood pressure, heart rate and sympathetic nerve activity were significantly larger in DOCA-salt hypertensive rats than those in sham operated rats. In contrast, percent changes in blood pressure and sympathetic nerve activity were not significantly different between spontaneously hypertensive rats and normotensive wistar kyoto rats. These result show that the responses of blood pressure, heart rate and sympathetic nerve activity to intracerebroventricular taurine are different between spontaneously hypertensive rats and DOCA-salt hypertensive rats. It appears that augmented vasodepressor responses to taurine in DOCA-salt hypertensive rats, as compared to spontaneously hypertensive rats, are due to enhanced inhibition of the sympathetic outflow.     

Impaired cardiac ischemic tolerance in spontaneously hypertensive rats is attenuated by adaptation to chronic and acute stress

Chronic hypertension may have a negative impact on the myocardial response to ischemia. On the other hand, intrinsic ischemic tolerance may persist even in the pathologically altered hearts of hypertensive animals, and may be modified by short- or long-term adaptation to different stressful conditions. The effects of long-term limitation of living space (ie, crowding stress [CS]) and brief ischemia-induced stress on cardiac response to ischemia/reperfusion (I/R) injury are not yet fully characterized in hypertensive subjects. The present study was designed to test the influence of chronic and acute stress on the myocardial response to I/R in spontaneously hypertensive rats (SHR) compared with their effects in normotensive counterparts. In both groups, chronic, eight-week CS was induced by caging five rats per cage in cages designed for two rats (200 cm²/rat), while controls (C) were housed four to a cage in cages designed for six animals (480 cm²/rat). Acute stress was evoked by one cycle of I/R (5 min each, ischemic preconditioning) before sustained I/R in isolated Langendorff-perfused hearts of normotensive and SHR rats. At baseline conditions, the effects of CS were manifested only as a further increase in blood pressure in SHR, and by marked limitation of coronary perfusion in normotensive animals, while no changes in heart mechanical function were observed in any of the groups. Postischemic recovery of contractile function, severity of ventricular arrhythmias and lethal injury (infarction size) were worsened in the hypertrophied hearts of C-SHR compared with normotensive C. However, myo-cardial stunning and reperfusion-induced ventricular arrhythmias were attenuated by CS in SHR, which was different from deterioration of I/R injury in the hearts of normotensive animals. In contrast, ischemic preconditioning conferred an effective protection against I/R in both groups, although the extent of anti-infarct and anti-arrhythmic effects was lower in SHR. Both forms of stress may improve the altered response to ischemia in hypertensive subjects. In contrast to short-term preconditioning stress, chronic psychosocial stress was associated with a higher risk of lethal arrhythmias and contractile failure in normotensive animals exposed to an acute ischemic challenge.     

Role of renin-angiotensin system in the impairment of baroreflex control of heart rate in renal hypertension.

Studies of the baroreceptor heart rate reflex were performed in two-kidney, one clip (2K1C) hypertensive rats to evaluate the relative importance of two factors--high blood pressure and high angiotensin II circulating levels--on impairment of the baroreflex, present in the acute phase of this model of hypertension. The sensitivity of baroreceptor reflex was determined by the slope of the relationship between changes in mean arterial pressure (MAP) and changes in heart rate in response to injections of phenylephrine and nitroprusside. Bradycardic and tachycardic responses were analyzed separately. In basal conditions, the slope of the MAP-heart rate relationship in 2K1C hypertensive animals was significantly lower than in control animals, both for tachycardic and bradycardic responses. Lowering of blood pressure with captopril to normotensive levels in the 2K1C animals significantly increased baroreflex gain in bradycardic responses to the level found in normotensive rats. Normalization of blood pressure with nitroprusside did not change baroreflex sensitivity. Infusion of angiotensin II at a dose that did not change MAP, previously normalized with captopril, completely reverted the effect of this agent on baroreflex sensitivity. Our data indicate that, in 2K1C hypertensive rats, decreased baroreflex sensitivity is mediated, at least in part, by high angiotensin II circulating levels. Elevated blood pressure per se is of secondary importance.     

Erythrocyte Sodium - Lithium Countertransport in Chinese: Its Relationship to Family History of Hypertension

Rates of sodium (Na⁺) - stimulated lithium (Li ⁺) efflux (Na⁺-Li⁺ countertransport) and ouabain-sensitive Na⁺ efflux (Na⁺ pump) were determined in erythrocytes of Chinese normotensive and hypertensive subjects. Near-maximal rate of Na⁺ - Li⁺ countertransport was found to be significantly higher in hypertensive than normotensive subjects. No significant difference was observed for the rate of Na⁺ pump between them. A second series of study involved normotensive subjects without and with hypertensive parent(s) (group A and B, respectively) and hypertensive subjects (group C). We found that the rate of Na⁺ - Li⁺ countertransport in group A was significantly lower than that of group B and C, while no difference existed between group B and C. No significant difference was observed for the rate of Na⁺ pump among the three groups. Our results suggested that Na⁺-Li⁺ countertransport activity could be a genetic marker for essential hypertension in Chinese, similar to that as proposed in Caucasians.     

Alterations in circulating levels and cardiovascular tissue content of neuropeptide Y-like immunoreactivity during the development of deoxycorticosterone acetate-salt hypertension in the rat.

OBJECTIVE: To investigate the modification of plasma and tissue neuropeptide Y-like immunoreactivity (NPY-li) concentrations, in relation to blood pressure and plasma catecholamine levels, during the development of deoxycorticosterone acetate (DOCA)-salt hypertension. METHODS: Mean arterial pressure (MAP), heart rate, tissue and plasma NPY-li levels, and aortic norepinephrine and epinephrine plasma levels were measured in conscious DOCA-salt hypertensive rats treated for 1, 2 and 3 weeks, and in their respective normotensive controls. RESULTS: Both norepinephrine and NPY-li plasma levels increased significantly in parallel with blood pressure during DOCA-salt treatment, so that MAP was significantly correlated with plasma norepinephrine and NPY-li levels in hypertensive rats. Plasma NPY-li levels were also correlated with norepinephrine levels only in hypertensive rats, but were correlated with epinephrine levels only in normotensive animals. Tissue NPY-li content was lower in the mesenteric artery and heart ventricles after 1-3 weeks of DOCA-salt treatment, but the content in the adrenal gland was not significantly different from that in normotensive rats. CONCLUSIONS: In DOCA-salt hypertensive rats, increased plasma NPY-li levels originate primarily from the sympathetic nerves, since those levels were correlated exclusively with circulating norepinephrine levels and they were associated with a reduction in NPY-li content of the heart and mesenteric artery. It is thus possible that the enhanced release of NPY-li from sympathetic nerves could contribute to the rise in blood pressure and to the maintenance of hypertension in this experimental model.     

Attenuation of Intrinsic Active Tone by Endothelium-Derived Nitric Oxide in Aortae of Spontaneously Hypertensive Rats with Different Levels of Blood Pressure

The influences of endothelium on the basal tone of aortae from various strains of spontaneously hypertensive rats with different blood pressure (SHR, SHRSP, MSHRSP) were studied. Endothelium-intact preparations of aortac from spontaneously hypertensive rats exhibited spontaneous active tone, which was greater in the order of SHR < SHRSP < M-SHRSP. The active tone of the MSHRSP preparations was about 40% of high-K⁺-induced contraction, while that of normotensive WKY was less than 5%. The active tone was enhanced by the removal of endothelium. The active tone was sensitive to extracellular Ca²⁺ and abolished by verapamil. The application of N^G-monomethyl-L-arginine caused the increase in the active tone which was counteracted by L-arginine. These results indicate that the active tone of smooth muscle increases as the blood pressure of the rat increases, and that endothelium attenuates the active tone by releasing nitric oxide (NO) spontaneously. It was also demonstrated that the attenuating action of endothelium was impaired depending on the blood pressure level.     

Antihypertensive effect of cardiovascular Ca2+-antagonist in hypertensive patients in the absence and presence of beta-adrenergic blockade

The effect of the administration of a cardiovascular Ca²⁺-antagonist (nifedipine) on arterial blood pressure, heart rate, and plasma renin activity was investigated.Blood pressure of normotensive healthy volunteers (n = 4) does not change significantly by administration of 10 mg. (from $\text{119}\text{78}\text{to}\text{120}\text{75}\text{mm. Hg}$) and 30 mg. (from $\text{114}\text{69}\text{to}\text{105}\text{66}\text{mm. Hg}$) of nifedipine. When nifedipine (30 mg.) is administered with propranolol (beta-blockade), a slight decrease of systolic and diastolic blood pressure was observed (from $\text{119}\text{73}\text{to}\text{104}\text{67}\text{mm. Hg}$). Blood pressure of hypertensive patients is significantly lowered by 10 mg. of nifedipine from 172.9 to 130.3 mm. Hg (25 per cent reduction) systolic, and from 112.9 to 86.6 mm. Hg (23 per cent) diastolic (n = 7). Thirty mg. nifedipine had a slightly stronger hypotensive effect, namely 27 per cent reduction in systolic and 28 per cent in diastolic values (n = 9). Combined administration of nifedipine and propranolol, resulted in lowering initial blood pressure by 32 per cent and 30 per cent reduction in systolic and diastolic (n = 8), respectively.The heart rate of normotensive patients hardly changes with administration of 10 and 30 mg. of nifedipine and combined medication. But in hypertensive subjects it is significantly increased by nifedipine; from 66.3 to 80.3 (p < 0.001) by 10 mg., and from 70.0 to 82.2 beats/minute (p < 0.01) by 30 mg. On the contrary, combined administration of nifedipine and propranolol causes no increase or only a slight decrease in heart rate (from 68 to 66 beats/minute).Plasma renin activity of normotensive and hypertensive subjects is increased by 30 mg. of nifedipine. Combined administration of nifedipine and propranolol decreases plasma renin activity in both normotensive and hypertensive patients.The antihypertensive effect of nifedipine is enhanced and prolonged by propranolol. The observed increase in heart rate and plasma renin activity with nifedipine is inhibited by propranolol, probably by inhibiting the cardiovascular effects of the activity of the sympathetic nervous system.The results of this study indicate that oral administration of nifedipine is very effective in lowering arterial blood pressure in hypertensive patients, especially when combined with propranolol.Administration of nifedipine with beta-blockade resulted in satisfactory management of hypertension with minimal adverse drug reactions which could be possibly attributed to the preparation, especially in the management of hypertensive emergencies including hypertension associated with acute myocardial infarction and coronary insufficiency.     

The Role of Vascular Protein and Renin in Chronic Two-Kidney,One Clip Goldblatt Hypertension

Chronic hypertension was induced in rats by application of a clip for 17 or 20 weeks to the unilateral renal artery and leaving the contrarenal vessel intact (two-kidney one clip hypertension, 2K-1C hypertension). Some of the rats received antihypertensive treatment with phenoxybenzamine (POB). ³H-proline was injected into all rats in the 17th experimental week to observe the in vivo incorporation rates of ³H-proline into vascular non-collagenous protein and vascular collagen. Plasma renin activity (PRA) of decapitated rats was assayed in the terminal stage of the experiment.

Significant differences were noted between 2K-1C hypertensive rats and sham-operated normotensive rats, the former rats having significantly higher incorporation rates of ³H-proline into non-collagenous protein (p<0.001) and collagen of testicular (p<0.05) or mesenteric artery (p<0.01). The ³H-proline incorporated into each fraction of vascular protein was reduced by antihypertensive treatment with POB either in sham-operated rats (p<0.05) or 2K-1C rats (p<0.001), except for the aorta and heart. Positive correlations were noted between blood pressure and incorporated ³H-proline into non-collagenous protein of testicular arteries (r=0.78, p<0.001) and mesenteric arteries (r=0.90, p<0.001), in all animals. Similar positive correlations were also noted between blood pressure and tritiated collagen, to lesser extents, in testicular arteries (r=0.67, p<0.001) and mesenteric arteries (r=0.73, p<0.001). A rapid turnover of ³H-proline incorporated into non-collagenous protein was characteristically observed in the testicular arteries, mesenteric arteries and aorta of 2K-1C hypertensive rats 3 weeks after the proline injection. Though magnitude was low, the turnover of %-proline was also noted in each collagen fraction of the equivalent vessels of the same hypertensive rats.

PRA of 2K-lC hypertensive rats was similar to that of shamoperated normotensive rats at the 20th week. Levels of PRA of the former or the latter rats treated with POB were 2.4-fold (p<0.001) or 2.5-fold (p<0.001) higher than those of non-medicated corresponding controls.

These results indicate that (1) increased synthesis of vascular non-collagenous protein as well as collagen, especially of small arteries, plays a major role for the pathogensis of chronic hypertension in 2k–lC rats and (2) renin does not contribute to elevation of the blood pressure in the maintenance phase of this type of experimental hypertension.     

Different effects of captopril on blood pressure in the acute and chronic two-kidney Goldblatt hypertensive dogs

Captopril was administered to acute (8 to 14 days after unilateral renal artery constriction) and chronic (71 to 127 days after the constriction) two-kidney Goldblatt hypertensive dogs, and to normotensive ones for 21 days (oral administration of 10, 20 and 40 mg/kg/day, consecutively each 7-day period). The decrease of arterial blood pressure was remarkable in hypertensive animals with high plasma renin activity, but not in the normotensive animals. In the acute stage of hypertension, the antihypertensive effect of captopril was dose-dependent and persistent even after its cessation. In the chronic stage of hypertension, blood pressure also decreased, but the response was not dose-dependent and did not continue after cessation. Plasma renin activity rose in both hypertensive and normotensive animals during the treatment with captopril. There were no significant changes in heart rate, daily urinary volume, sodium balance, and renal clearances of sodium (CNa), potassium (CK), chloride (CCl) and creatinine (CCr). Circulating blood volume was also not altered. These results indicate that the main mechanism of antihypertensive effect of captopril in two-kidney Goldblatt hypertensive dogs is an inhibition of the angiotensin converting enzyme. In addition, the different effects in the acute and chronic hypertensive dogs suggest that some differences exist in the mechanism(s) of maintaining blood pressure between the two stages of two-kidney Goldblatt hypertension in dogs.     

Failure of atriopeptin II to cause arterial vasodilation in the conscious rat

The cardiovascular actions of the synthetic natriuretic peptide, atriopeptin II, were examined in conscious unrestrained spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The animals were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow, or with an electromagnetic flow probe on the ascending aorta to facilitate the measurement of cardiac output in the conscious rat. Intravenous infusion of increasing doses of atriopeptin II (0.25-4 micrograms/kg per min) caused a dose-dependent fall in mean arterial pressure in the hypertensive and normotensive rats. Blood flow in the renal, mesenteric, and hindquarters vascular beds was markedly decreased during the infusion of atriopeptin II, and regional vascular resistance was significantly increased in both groups of rats. Heart rate was significantly elevated (47 +/- 14 beats/min) in the spontaneously hypertensive rats during atriopeptin II infusion, but no change in heart rate was observed in the Wistar rats. In the hypertensive rats, atriopeptin II caused a marked dose-dependent decrease in cardiac output (maximal decrease = -39 +/- 4%) and stroke volume (maximal decrease = -48 +/- 4%). Central venous pressure and left atrial pressure were also significantly reduced during atriopeptin II infusion. Total peripheral resistance was increased over the infusion protocol by 26 +/- 3%. These data suggest that atriopeptin II infusion markedly attenuated cardiac output in the conscious spontaneously hypertensive rats. Total and regional vascular resistances were increased, possibly through reflex compensatory mechanisms, to maintain arterial pressure in the face of decreased cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of atrial natriuretic factor on blood pressure, heart rate, and renal functions in conscious, spontaneously hypertensive rats

Atrial natriuretic factors, polypeptides released by atrial myocytes, may play a role in the control of blood pressure and the regulation of renal salt and water excretion. Our studies were designed to assess the role of a synthetic peptide, atriopeptin II, on blood pressure and heart rate, renal hemodynamics, and salt and water excretion in conscious, spontaneously hypertensive rats and in normotensive Wistar-Kyoto rats. Changes in mean arterial pressure and heart rate were recorded following intravenous bolus injections (0.1, 1.0, 10, 100 micrograms/kg) of atriopeptin II in 5 spontaneously hypertensive and 5 Wistar-Kyoto rats. In a second group of rats the peptide was infused for 90 minutes in two different doses: low dose, 1 microgram/kg + 2 micrograms/kg/hr; and high dose, 10 micrograms/kg + 20 micrograms/kg/hr. Bolus injections of atriopeptin II resulted in dose-dependent decreases in mean arterial pressure in the hypertensive, but not in the normotensive, rats; heart rates remained unchanged. Blood pressure decreased gradually during the sustained infusion of both doses of atriopeptin II, with the spontaneously hypertensive strain showing increased sensitivity compared to the Wistar-Kyoto strain. Heart rate decreased in both strains during infusion of the high dose; the decrease was significant only in the hypertensive rats. The low dose of atriopeptin II increased the clearance of free water in both strains of rats; sodium excretion was increased only in the hypertensive rats. The high-dose atriopeptin II was associated with transient natriuresis, unaltered glomerular filtration rate, and decreased effective renal blood flow in both strains.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transection of aortic depressor nerve fails to raise blood pressure in spontaneously hypertensive rats

Although central resetting via the aortic depressor nerve (ADN) has been known to occur in spontaneously hypertensive rats, the function of the ADN is not yet clear in these animals. To determine whether a baroreflex via the ADN can act to regulate blood pressure during hypertension, blood pressures were measured following ADN transection in spontaneously hypertensive and normotensive rats, and the reflex changes of heart rate and the sympathetic nerve activity were recorded during the pressor response to phenylephrine infusions. Blood pressures were significantly raised 1 day after ADN transections in normotensive rats and continued so for 7 d. Blood pressures were not changed in sham operated rats. In spontaneously hypertensive rats, ADN transections did not alter blood pressures in comparison with sham operated controls. On the seventh day after transections, all rats were anaesthetised with urethane and pressor responses to phenylephrine were examined. Bradycardic and sympathoinhibitory responses to the elevation of blood pressure caused by phenylephrine infusions were significantly smaller in ADN transectioned normotensive rats than in sham operated controls. In spontaneously hypertensive rats, the bradycardic and sympatho-inhibitory responses were not reduced by ADN transections. These findings suggest that the impaired baroreflex via the ADN can contribute to the development of hypertension in the spontaneously hypertensive rat.     

EFFECTS OF NG-NITRO-L-ARGININE ON THE BLOOD PRESSURE OF SPONTANEOUSLY HYPERTENSIVE RATS WITH DIFFERENT DEGREES OF HYPERTENSION

The effects of N^G-nitro-L-arginine (L-NNA) on blood pressure of various strains of spontaneously hypertensive rats were studied. Blood pressure of the rats was higher in the order of WKY, SHR, SHRSP, M-SHRSP. L-NNA caused an elevation of the blood pressure, which was greatest in SHR and smallest in WKY and M-SHRSP. Endothelium-dependent relaxation of aortae by acetylcholine was greatest in preparations from WKY and it decreased as the blood pressure of rats increased. Phenylephrine (higher than 10^?6mg/kg) caused an elevation of the blood pressure, which was greatest in SHR and smallest in M-SHRSP. It was suggested that L-NNA elevated blood pressure by inhibiting the basal or flow-induced release of nitric oxide from the endothelium that is causing a reduction in vascular smooth muscle tone. The smaller effect of L-NNA in WKY was due to weak smooth muscle tone, while the smaller effect in SHRSP and M-SHRSP is due to impaired function of endothelium.     

Comparison of Norepinephrine Release in Hypertensive Rats: I Hypothalamic and Brainstem Tissues

Stimulation induced ³H-norepinephrine release was measured in hypothalamus and brainstem of spontaneously hypertensive (SHR) and normotensive (WKY) rats. Age dependent changes in ³H-norepinephrine release were shown to occur in the anterior and posterior hypothalamus and the A₂ region of the nucleus tractus solitarius (NTS). In an attempt to determine whether these changes in ³H-trasmitter release were causal or merely secondary to the increase in blood pressure, similar release studies were carried out in DOCA-salt and one kidney-one clip hypertensive animals with similar levels of systolic blood pressure. The changes in stimulus-induced ³H-norepinephrine release seen in the SHR were not observed in the other two models of hypertension, suggesting that one: they were not secondary to an increase in systolic blood pressure; and two that the changes observed in the SHR may possibly play a role in the development and/or maintenance of the hypertension.     

Effect of Plasma from Essential Hypertensives on Tension of Aortic Strips

The effect of fractions of plasma from essential hypertensive (n=27) and normotensive subjects (n=26) on the tension of aortic strips (n=27) from normotensive rats was examined. The fractions obtained from hypertensive patients had been shown to increase blood pressure, when injected intravenously in a normotensive rat. In aortic strips the hypertensive fractions elicited a translent relaxation of variable amplitude and subsequently a sustained contraction. The normotensive fractions did not alter tension of the strips significantly. In Ca²⁺ free medium and after addition of nifedipine hypertensive plasma fractions did not induce a contraction, whereas in Na⁺ free medium the contraction was not abolished. It is concluded that in the fraction of hypertensive plasma containing substances with a molecular weight in the range of 1000 - 1500 Da a vasopressor agent with direct actions on arterial smooth muscle is present. The substance probably acts by increasing Ca²⁺ influx in vascular smooth muscle.