Morphometric study of cerebral arteries from spontaneously hypertensive and stroke-prone spontaneously hypertensive rats.

OBJECTIVE: The importance of sympathetic innervation for the development of structural changes in the cerebral arteries of hypertensive animals was studied. DESIGN: Sympathetic denervation was induced with combined treatment from birth of antibody against nerve growth factor and guanethidine. Previous studies from our laboratory showed that this procedure not only caused a permanent denervation of the mesenteric arteries, but also prevented the development of hypertension in spontaneously hypertensive rats (SHR). METHODS: Morphometric measurement of the structural changes was carried out in the basilar, superior cerebellar, posterior cerebral and middle cerebral arteries from 28-week-old SHR, stroke-prone SHR, and normotensive Wistar-Kyoto rats. The results were compared with those obtained from cerebral arteries of sympathectomized rats. RESULTS: Total vascular wall cross-sectional area was significantly larger in the basilar and superior cerebellar arteries from hypertensive rats compared with normotensives. The change was characterized by an increase in the number of smooth muscle cell layers. There were also differences between the two hypertensive groups in some arteries. Sympathetic denervation attenuated the development of hypertension and vascular changes in some arteries. There was a positive linear correlation between blood pressure and medial cross-sectional area, and between blood pressure and the number of smooth muscle cell layers for the four arteries analysed. CONCLUSION: Sympathetic nerves have a trophic influence upon the remodelling of some cerebral arteries during the development of genetic hypertension.     

Caffeine-induced contraction in arteries from stroke-prone spontaneously hypertensive rats

Differences in caffeine-induced contraction in smooth muscle of resistance vessels from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) were investigated by using mesenteric artery preparations. The contraction induced by caffeine (10 mM) was greater in SHRSP preparations, both in the presence and absence of Ca (10 min after Ca removal). Caffeine-induced contraction was gradually decreased by the removal of extracellular Ca. No significant difference was observed in the time course of the decay of the contraction between SHRSP and WKY preparations, and the contraction disappeared when the time in Ca-free solution exceeded 80 min. The contraction induced by high-K-Tyrode's solution was completely abolished within 10 min after Ca removal, both in SHRSP and WKY preparations. Caffeine-induced contraction could be blocked by procaine or ryanodine. The results suggest that caffeine induces contraction by releasing Ca from sarcoplasmic reticulum, and that the release of Ca is greater in SHRSP vascular smooth muscle. It is also suggested that sarcoplasmic reticulum is leaky for stored Ca when extracellular Ca is removed, and that the rate of leakage does not differ between smooth muscle cells of SHRSP and WKY mesenteric arteries.     

Enhanced angiotensin converting enzyme binding in arteries from spontaneously hypertensive rats.

AIM: To localize and measure angiotensin converting enzyme (ACE) in different vascular beds of genetically hypertensive rats. METHODS: Quantitative autoradiography using the angiotensin converting enzyme (E.C. 3.4.15.1) inhibitor [125I]351A. RESULTS: [125I]351A binding was significantly increased in the ascending aorta (both adventitia and intima), descending (abdominal) aorta, carotid artery and coronary arteries of adult, 12-week-old spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats. Increased [125I]351A binding was also present in the descending aorta of 1-week-old SHR compared with age-matched WKY rats, and both groups of young rats had much higher binding than adult rats. No difference in [125I]351A binding was found in the caudal (tail) artery of adult SHR compared with WKY rats. In both the atria and the ventricles of adult SHR, [125I]351A binding was very significantly reduced. CONCLUSIONS: Our results indicate that higher ACE concentrations occur in some arteries of genetically hypertensive rats, and support the hypothesis that local arterial concentrations of ACE affect the development and maintenance of genetic hypertension.     

Ultrastructural changes in mesenteric arteries from spontaneously hypertensive rats. A morphometric study

Morphometric measurements at the electron microscope level were carried out on three categories of mesenteric arteries representing elastic (superior mesenteric), muscular and arteriolar vessels, from 10- to 12-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto normotensive rats (WKY). Changes were observed only in muscular and arteriolar vessels of SHR, mainly as thickening of the vessel wall due to hypertrophy of the media. In muscular arteries, hypertrophy of the endothelial cells, widening of the subendothelial space, increased volume of the internal elastic lamina (IEL), and both hyperplasia and hypertrophy of the smooth muscle cells (SMC) in the media contributed to the wall thickening. In arteriolar vessels, increase in the subendothelial space and IEL, and hyperplasia of the SMC in the media were involved in the increased thickness of the vessel wall. There was no difference in the collagen content in all vessels, but elastin was increased in the muscular and arteriolar vessels of SHR. Nerve density was also increased in arteriolar vessels of SHR. These changes, especially the increase of SMC in muscular and arteriolar vessels, may be related to the elevated blood pressure in SHR.     

Profile of pregnancy in young spontaneously hypertensive rats

The uterine contents and ovaries of pregnant spontaneously hypertensive rats (SHR) were compared to those of control Wistar-Kyoto rats (WKY). Although there were no strain differences in the number of released oocytes as indicated by corpora lutea, there were fewer viable fetuses in the SHR litters compared to WKY. Since there was no difference in post-implantation intrauterine loss, the lower SHR fetal number was most likely due to fewer successful implantations in the SHR. Maternal blood pressures declined significantly in both strains on day 18 of gestation.     

Vascular changes at the prehypertensive phase in the mesenteric arteries from spontaneously hypertensive rats

Morphometric measurements of three categories of mesenteric vessels (representing elastic, muscular and arteriolar vessels) from prehypertensive spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) were carried out at the light and electron microscope levels. Structural alterations of the blood vessels were already present in the SHR, even though the blood pressure was not yet elevated as compared with age-matched WKY. No change was found in the elastic vessels (superior mesenteric artery). Among the muscular arteries (i.e. large mesenteric arteries), the increase in vessel wall cross-sectional area was due to the increase in the intima, media and adventitia. Increase in media was due to hyperplasia of the smooth muscle cells. The smooth muscle cells were not hypertrophied. Nerve density was also higher in the large mesenteric arteries of SHR. In the arteriolar vessels (i.e. small mesenteric arteries), wall to lumen ratio, as well as media to lumen ratio, were increased in the SHR. The number of smooth muscle cell layers was also increased. In all these vessel types, the cross-sectional area of the lumen under maximal relaxation was similar between SHR and WKY, except in small mesenteric arteries where the lumen was smaller in the SHR. Our results suggest that structural alteration of the blood vessels at the prehypertensive phase may be one of the contributing factors leading to the development of hypertension in the SHR.     

Hepatic arteries in normotensive and spontaneously hypertensive rats. A morphometric study

The media thickness (m), luminal radius (r) and m/r ratio were determined in the hepatic arterial trunk and in intra-hepatic arterial branches as was the number of arteries per cm2 sectioned liver tissue in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto controls (WKY). The cross-sectional vessel parameters were calculated for a standardized condition, in which the internal elastic membrane is smooth and circular. Both intra-hepatic arterial branches and the hepatic arterial trunk showed significantly higher m/r ratios in SHR than in WKY controls. The luminal radius of the hepatic arterial trunk was larger in SHR than in WKY (P less than 0.05). The number of arteries per cm2 sectioned liver tissue was greater in SHR (P less than 0.05). It is suggested that the consequences of the increased m/r ratio in hepatic arteries of SHR are counteracted to some extent by an increased vascularization, but that during hypovolaemia and compensatory vasoconstriction, a greater decrease in hepatic arterial blood flow occurs in SHR than in WKY.     

Enhanced myogenic responsiveness of renal interlobular arteries in spontaneously hypertensive rats.

We recently demonstrated that the interlobular artery (ILA) constricts in response to elevating renal arterial pressure (RAP), suggesting that the ILA contributes to renal autoregulation. In the present study, we examined the segmental myogenic responsiveness of the ILA in kidneys from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The tapered nature of the ILA allowed us to characterize the regional responsiveness, using the basal diameter to define segments as either proximal (greater than 60 microns), intermediate (40-60 microns), or distal (less than 40 microns). At 80 mm Hg, segmental diameters were similar in WKY and SHR arteries (proximal, 76.0 +/- 3.1 versus 71.6 +/- 3.5 microns; intermediate, 48.2 +/- 1.4 versus 48.1 +/- 1.7 microns; distal, 30.7 +/- 0.9 versus 27.9 +/- 1.3 microns for WKY and SHR, respectively). In both strains, intermediate and distal segments exhibited graded reductions in diameter as RAP was elevated, whereas proximal segments did not. Pressure-induced decrements in the diameters of distal ILA segments were similar in WKY (-24 +/- 2%) and SHR (-20 +/- 2%; p greater than 0.1). The intermediate ILA of SHR exhibited an augmented myogenic responsiveness, constricting at lower RAP levels and exhibiting greater maximal decrements in diameter at 180 mm Hg (i.e., -19 +/- 2% and -12 +/- 2% for SHR and WKY, respectively; p less than 0.05). Nifedipine (1.0 microM) reduced pressure-induced vasoconstriction of intermediate and distal ILA segments by 56 +/- 11% and 79 +/- 7%, respectively, in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)     

Norepinephrine overflow in perfused mesenteric arteries of spontaneously hypertensive rats

We examined the overflow of endogenous norepinephrine with electrical stimulation, the associated pressor response, and rate of initial neuronal uptake of [3H]norepinephrine in perfused mesenteric arteries of 7- and 13-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The tissues of two rats, a spontaneously hypertensive and a WKY control rat, were simultaneously processed and subjected to the same electrical stimulation. Both absolute and fractional overflow of endogenous norepinephrine during periarterial nerve stimulation (5 and 10 Hz for 1 minute) in the tissue of 7-week-old SHR was significantly greater whereas overflow of 13-week-old SHR was equivalent as compared with that of the age-matched WKY rats. The tissue content of norepinephrine was 20-25% higher in SHR of both ages. There was significantly enhanced [3H]norepinephrine uptake in the tissues of young SHR, but no difference was observed in the older SHR. The pressor response to periarterial nerve stimulation was significantly enhanced in 7-week-old SHR and much more so at the older age as compared with the WKY control rats. Exogenous norepinephrine dose-response curves in the tissues of 7-week-old SHR exhibited a parallel leftward shift, characteristic of a change in sensitivity, whereas that of 13-week-old SHR showed a much steeper slope as compared with the respective WKY control rats. This finding suggests that in addition to smooth muscle supersensitivity, structural alterations had occurred in vasculature of 13-week-old SHR. These data indicate that in SHR both the exocytotic release of norepinephrine and the responsiveness of the vascular smooth muscle cells are enhanced in the developmental stage of hypertension whereas smooth muscle supersensitivity to norepinephrine and nonspecific structural alterations primarily contribute to the maintenance of hypertension at 13 weeks of age.     

Characterization of endothelium-dependent vasodilation and vasoconstriction in coronary arteries from spontaneously hypertensive rats

Coronary artery disease often occurs in patients with hypertension. The present study was designed to evaluate coronary vascular function in isolated coronary arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats and to determine the effect of antihypertensive treatment on coronary vascular responsiveness. Male SHR and WKY rats (12 to 14 weeks old) were divided into control and hydralazine-treated (120 mg/L drinking water for 10 days) groups. After 10 days, arterial pressure and heart rate were recorded while rats were conscious and unrestrained. Left ventricular coronary arteries (200 to 300 μm diameter) were isolated and intraluminal diameter was continuously recorded while vessels were maintained at a constant intraluminal pressure of 40 mm Hg. Relaxation of coronary arteries to both acetylcholine and nitroprusside was slightly, but significantly, enhanced in vessels from SHR compared to WKY rats. The enhanced relaxation was a specific effect, since isoproterenol induced similar relaxation in coronary arteries from SHR and WKY rats. Contraction to phenylephrine, but not endothelin-1, was augmented in coronary arteries from SHR compared to WKY rats. Treatment with hydralazine significantly lowered arterial pressure in SHR and WKY rats, but did not alter the enhanced contraction to phenylephrine or the enhanced relaxation to acetylcholine and nitroprusside in coronary arteries from SHR. These results indicate that coronary arteries of 12 to 14 week-old SHR do not have impaired endothelium-dependent relaxation, but do exhibit enhanced α-adrenoreceptor-mediated contraction that is not reduced by lowering arterial pressure.     

Decrease in alpha 1-adrenoceptor reserve in mesenteric arteries isolated from spontaneously hypertensive rats

The characterization of alpha-adrenoceptor-mediated contractile responses and the effects of the calcium channel blocker nifedipine on these responses were investigated in mesenteric arterial strips from 13-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Contractile responses to the alpha-adrenoceptor agonists phenylephrine and clonidine were mediated through the activation of alpha 1-adrenoceptors. The dose producing a half-maximum response (ED50) for the agonists was higher in SHR than in WKY. Affinities of alpha 1-adrenoceptors were similar between the two strains. When arterial strips from both strains were treated with the same concentration of phenoxybenzamine, the maximum response to each agonist was weaker in SHR. The alpha 1-adrenoceptor occupancy-response relationship for phenylephrine was hyperbolic and less steep in SHR, while the relationship for clonidine was linear in SHR but not in WKY. Alpha 1-adrenoceptor occupancy at a half-maximum response to each agonist was greater in SHR. Nifedipine inhibited the maximum responses to the agonists more profoundly in SHR than in WKY. This inhibition was greater in the response to clonidine than in the response to phenylephrine in both strains. When the maximum response to phenylephrine was reduced to the same extent in both strains by treatment with different concentrations of phenoxybenzamine, the responses to phenylephrine were more susceptible to inhibition by nifedipine. Under these conditions, the effects of nifedipine were similar between SHR and WKY. These results suggest that alpha 1-adrenoceptor reserve is reduced in SHR mesenteric artery compared with WKY, which may be responsible for the greater inhibition by nifedipine of the alpha 1-adrenoceptor-mediated contractions in SHR.     

Left ventricular hypertrophy and its reversibility in young spontaneously hypertensive rats.

The development of an increased ventricular wall mass was followed from birth until five weeks of age and also later in life in spontaneously hypertensive rats (SHR) which were compared with normotensive control rats (NCR). It was shown that the first signs of enhanced ventricular growth were already evident in SHR in the first week of life. At 10 months of age left ventricular weight was 68% higher in SHR than in matched NCR, at a mean pressure difference of 30%. Treatment of SHR with antihypertensive agents, like hydralazine, hydralazine-guanethidine, propranolol, or metoprolol, from three weeks up to 10 months of age reduced this gross increase in left ventricular weight by only about 10% while the mean pressure difference between SHR and NCR was reduced by 50 to 70%. It appears that the increase in left ventricular wall mass in SHR is initiated so early in life and is of such a character that it can only, to a fairly minor extent, be reversed or prevented by pressure-lowering procedures. Part of the explanation may be a substantial contribution of myocardial hyperplasia, in association with a genetically linked predisposal to structural cardiovascular adaptation, either 'inherent' in the effectors and/or caused by 'trophic' influences of a hormonal and/or transmitter nature.     

Specific changes in hypothalamic alpha-adrenoceptors in young spontaneously hypertensive rats

Changes in the activity of hypothalamic and brain-stem adrenergic neurons have been reported in young spontaneously hypertensive rats (SHR) prior to the development of hypertension. We have measured central alpha- and beta-adrenoceptor concentrations in 4-week-old SHR and Wistar-Kyoto (WKY) controls by direct radioligand binding studies using [3H]prazosin (alpha 1), [3H]clonidine (alpha 2), and [125I]iodohydroxybenzlpindolol (beta). The concentration of alpha 2-adrenoceptors was significantly elevated in the hypothalamus of the SHR, 156.9 +/- 10.4 compared with WKY, 119.4 +/- 10.0 fmole/mg protein (n = 7, mean +/- SEM, p less than 0.0125). Alpha 2-adrenoceptor concentrations in both the brain stem and cerebral cortex were similar in the two groups of animals. The increase in hypothalamic adrenoceptors was specific for alpha 2-adrenoceptors, since similar concentrations of alpha 2- and beta-adrenoceptors were found in this region.     

Enhanced neuropeptide Y immunoreactivity and vasoconstriction in mesenteric small arteries from spontaneously hypertensive rats

Enhanced sympathetic nerve activity is thought to play a role in the pathogenesis of hypertension. The purpose of the present study was to investigate the mechanisms underlying the enhanced vasocontractile response to perivascular stimulation of mesenteric arteries isolated from female spontaneously hypertensive rats (SHR). Innervation of mesenteric small arteries was evaluated by immunohistochemistry and confocal microscopy while functional studies were conducted in a microvascular myograph. The distribution of nerve terminals immunoreactive for tyrosine hydroxylase (TH) and neuropeptide Y (NPY) was similar in mesenteric small arteries from Wistar-Kyoto (WKY) and SHR rats. However, immunointensity of TH or NPY immunoreactivities were much higher in small arteries from SHR compared to WKY. Expressed as percentage of contractions elicited by 124 mM K(+), concentration-response curves for noradrenaline (NA) and NPY were shifted leftward in SHR compared with WKY rats. The combination of noradrenaline (1 microM) and NPY (10 nM) contracted mesenteric arteries from WKY and SHR to higher levels than compared to either contractile agent added alone. The NPY Y(1) receptor antagonist, BIBP 3226, inhibited these contractions with 87 +/- 0.7 and 80 +/- 1.3% (p < 0.05, n = 6) in arteries from WKY and SHR rats, respectively. In arteries incubated with the alpha(1)-adrenoceptor antagonist, prazosin, and preactivated with vasopressin, electrical field stimulation evoked contractions which were more pronounced in mesenteric arteries from SHR compared to WKY rats. BIBP 3226 partially inhibited these contractions. In vasopressin-activated arteries BIBP 3226 caused rightward shifts of the concentration-response curves for NPY in mesenteric arteries from SHR rats, but in addition it also abolished the maximal NPY contraction in arteries from WKY rats. In the presence of BIBP 3226, low concentrations (1 pM to 10 nM) of NPY caused relaxations in arteries from WKY, but not in segments from SHR rats. Mechanical removal of the endothelium abolished NPY relaxation in arteries from WKY. In arteries activated with vasopressin and exposed to either forskolin or sodium nitroprusside, the addition of NPY evoked contractions which were more pronounced in arteries from SHR compared to WKY arteries. The present study suggests that enhanced NPY content and vasoconstriction to NPY in arteries from hypertensive rats can contribute to the enhanced sympathetic nerve activity and vascular resistance in female hypertensive rats. Endothelial cell dysfunction as well as alterations in smooth muscle response to NPY seem to contribute to the enhanced vasoconstriction in arteries from hypertensive animals.     

Increased oxidative stress impairs endothelial modulation of contractions in arteries from spontaneously hypertensive rats

OBJECTIVES: The endothelium modulates vascular contractions. We investigated the effects of oxidative stress on endothelial modulation of contractions in hypertension. METHODS: Changes in isometric tension of femoral arterial rings from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were recorded. RESULTS: The contractile response to norepinephrine of arteries with endothelium was greater in SHR than in WKY rats (P < 0.0001). Endothelium removal augmented the norepinephrine-induced contraction (P < 0.05). The augmentation was more pronounced in WKY than in SHR, which resulted in comparable contraction of arteries without endothelium in both strains. Nomega-nitro-L-arginine methyl ester (100 micromol/l) mimicked the effect of endothelium removal. Production of nitric oxide (NO, assessed by measuring nitrite/nitrate concentrations) during the contraction was not different between SHR and WKY. Vitamin C suppressed the contraction of arteries with endothelium from SHR but not from WKY (P < 0.05). Diphenyleneiodonium and apocynin, inhibitors of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase, attenuated the contraction of arteries with endothelium from SHR (P < 0.001) but not WKY, but did not affect contractions induced by serotonin. Superoxide generated by xanthine oxidase/hypoxanthine enhanced the norepinephrine-induced contraction of arteries with endothelium from WKY (P < 0.0001), and this effect was reversed by vitamin C. CONCLUSIONS: In rat femoral arteries, NO released from the endothelium modulates vascular contraction. In SHR, production of superoxide by NADH/NADPH oxidase, which may be activated by norepinephrine, is enhanced, resulting in the inactivation of NO and impairment of endothelial modulation of vascular contractions. Vascular oxidative stress may contribute to the altered circulation in hypertension by impairing endothelial modulation of vascular contractions.     

Eicosanoids and membrane properties in arteries of aged spontaneously hypertensive rats

OBJECTIVE: The arteries of aged spontaneously hypertensive rats (SHR) exhibit spontaneous electrical activity together with membrane depolarization. Vascular eicosanoid production is increased in SHR, which is further accelerated with aging. We tested the hypothesis that eicosanoids are involved in spontaneous electrical activity, membrane depolarization or both in mesenteric arteries of aged SHR. DESIGN AND METHODS: Membrane potentials were recorded with microelectrodes from the mesenteric arteries of aged (24 months and older) SHR, aged Wistar-Kyoto (WKY) rats and adult (6- to 8-month-old) SHR. RESULTS: The membrane potential was less negative in aged SHR (-38.5 +/- 0.9 mV) than in either aged WKY rats or adult SHR (-49.8 +/- 0.5 and -47.2 +/- 0.6 mV, respectively; P < 0.05 for both). Spontaneous electrical activity (5-20 mV, 1-7/min) was present only in arteries of aged SHR. Spontaneous electrical activity was not affected by phentolamine, atropine or tetrodotoxin, but was abolished by indomethacin, a cyclooxygenase inhibitor, and ONO-3708, a thromboxane A2/prostaglandin H2 receptor antagonist. Furthermore, indomethacin and ONO-3708 hyperpolarized the membrane by about 5 mV in aged SHR but not in the other two groups. Spontaneous electrical activity was enhanced by a thromboxane A2 analog and prostaglandin H2, and was abolished by a Ca2+ antagonist, nicardipine, and Ca(2+)-free solution. CONCLUSIONS: These findings suggest that cyclooxygenase-dependent eicosanoids contribute importantly to both spontaneous electrical activity and membrane depolarization, presumably through activation of the thromboxane A2/prostaglandin H2 receptor, in mesenteric arteries of aged SHR, and that spontaneous electrical activity is mediated by a Ca2+ influx through voltage-dependent Ca2+ channels.     

Elevated nerve growth factor levels in young spontaneously hypertensive rats

It is generally agreed that sympathetic innervation of vascular tissues in spontaneously hypertensive rats (SHR) is greater than that existing in vascular tissues from normotensive Wistar-Kyoto (WKY) rats. One factor responsible for regulation of the growth of peripheral sympathetic nerves is the peptide nerve growth factor, which is released from effector cells. In the present study, an enzyme immunoassay was used to measure nerve growth factor levels in mesenteric arteries (densely innervated) and aortas (sparsely innervated) from both young (20-day-old) and mature (6-month-old) SHR and WKY rats. The nerve growth factor content of mesenteric arteries and aortas from 20-day-old SHR was significantly greater than that present in corresponding tissues from WKY rats. In contrast, the nerve growth factor content found in mesenteric arteries and aortas of adult SHR did not differ significantly from that found in the corresponding adult WKY rat tissues. Moreover, when the tissues were obtained from adult animals, nerve growth factor levels were substantially higher in mesenteric arteries compared with aortas, regardless of the rat strain. These results support the hypothesis that the greater nerve growth factor content of vascular tissues from young SHR is involved in the early increased sympathetic innervation of blood vessels in this animal model of hypertension.     

Effects of salt-loading on membrane potentials in mesenteric arteries of spontaneously hypertensive rats.

Although salt intake and blood pressure are correlated, with hypertensives tending to exhibit higher blood pressure sensitivity to salt than normotensives, the precise mechanisms underlying this relationship remain unclear. This study aimed to determine whether salt-loading affects arterial membrane properties of spontaneously hypertensive rats (SHR). SHR and age-matched Wistar Kyoto rats (WKY) received either an 8% high salt diet or standard rat chow from 6 to 16 wk of age. Systolic blood pressure was significantly higher in salt-loaded SHR than in control SHR (267+/-7 vs. 235 +/- 5 mmHg, p < 0.05). The membrane potential of isolated conduit and resistance arteries of the superior mesenteric vascular bed, measured with microelectrodes, was less negative in salt-loaded SHR than in control SHR or salt-loaded WKY (conduit arteries, -39.9 +/- 0.3 vs. -44.5 +/- 0.4 or -47.4 +/- 0.4 mV, respectively, p < 0.05 for each; resistance arteries, -55.5 +/- 0.5 vs. -62.5 +/- 0.5 or -67.0 +/- 0.5 mV, respectively, p < 0.05 for each). Furthermore, conduit arteries of salt-loaded SHR exhibited spontaneous electrical activity (4-13 mV, 1-3/min), which was sensitive to ONO-3708, a thromboxane A2/prostaglandin H2 receptor antagonist. These findings suggest that salt-loading in SHR leads to a membrane depolarization in both conduit and resistance arteries, as well as to spontaneous electrical activity, presumably mediated by eicosanoids, in conduit arteries. These alterations in membrane properties might contribute to the exacerbation of hypertension and/or the target organ damage after salt loading in SHR.