Effect of indomethacin and deendothelisation on vascular responses in the renal artery

Vasodilator prostaglandins (PGE2, PGI2) play an important role in the regulation of renal blood flow. Hence, inhibition of their production with nonsteroidal anti-inflammatory drugs increases renal vascular resistance and exerts adverse renal effects. It has been reported that besides endothelium-derived prostaglandin products, nitric oxide (NO) may be mainly involved in regulation of renal functions. The aim of our study was to evaluate the effect of cyclooxygenase inhibition with indomethacin and endothelium removal on vascular responses of the renal artery as a model vessel. Isolated segments of rabbit renal arteries were perfused at constant flow. Indomethacin administration (10(-5) mol x l(-1)) significantly increased the responses to single doses (0.1, 1, 10 microg) of noradrenaline (NA) as compared with the controls. In indomethacin-pretreated vessels, subsequent deendothelisation by air bubbles enhanced the constrictor responses to NA. In reversed order, when deendothelisation was followed by indomethacin administration, the responses to NA were similar in character. A comparison of renal artery responses to NA in both experimental situations did not reveal any significant differences. It can be supposed that endothelial and non-endothelial factors may be involved in local regulation of renal vascular tone.     

Evaluation of endothelium-protective effects of drugs in experimental models of endothelial damage

Endothelium-protective properties of pharmacological agents may be assessed by using different experimental models of endothelial dysfunction or injury. The model of endothelial dysfunction induced by vessel perfusion with polymorphonuclear leukocytes (PMN) was used for evaluation of pentoxifylline (PTX) effects on vasoconstrictor responses to noradrenaline (NA) in the rabbit renal artery. Addition of PMN into the perfusion solution significantly increased the responses to NA at all doses. PTX administration (10(-5) mol x l(-1)) significantly diminished the constrictor responses to NA in vessels perfused with PMN+PTX when compared to the responses in PMN-perfused vessels (at dose 0.1 microg: 32.25 vs. 14.25, at dose 1 microg: 51 vs. 27.75 (p<0.01), at dose 10 microg 74.25 vs. 39.75 (p<0.05), all values expressed as median of perfusion pressure in mm Hg). The model of endothelial damage induced by repeated NA administration in 5 doses (10-50 microg of NA) was used for evaluation of the endothelium-protective effect of sulodexide (SLX). It was found that SLX (120 U/l) significantly decreased the number of desquamated endothelial cells (EC) compared to the control group (controls: 131.4+/-20.1 EC, +SLX: 83.3+/-13.8 EC, p<0.01). These results confirmed the favorable endothelium-protective effects of pentoxifylline and sulodexide in the two experimental models.     

Heterogeneous limb vascular responsiveness to shear stimuli during dynamic exercise in humans.

Arm and leg vascular responsiveness to comparable shear stimuli during isolated dynamic exercise has not been assessed in humans. Consequently, six young cyclists performed incremental, intermittent handgrip exercise (arm) and knee-extensor exercise (leg) from 5 to 60% of maximal work rate (WR). Ultrasound Doppler measurements were taken in the brachial artery (BA), common femoral artery (CFA), and deep femoral artery (DFA) at rest and at each WR to assess diameter and sheer rate changes. Exercise at 60% maximum WR increased shear rate to the same degree in the CFA (314.3 +/- 33.3 s(-1)) and BA (303.3 +/- 26.3 s(-1)), but was significantly higher in the DFA (712.6 +/- 88.3 s(-1)). Compared with rest, exercise at 60% maximum WR did not alter CFA vessel diameter, but increased BA diameter (0.42 +/- 0.01 to 0.49 +/- 0.01 cm) and DFA diameter (0.59 +/- 0.05 to 0.64 +/- 0.04 cm). These data from the DFA demonstrate for the first time a substantial improvement in vascular reactivity in a conduit vessel only slightly distal to the CFA. However, despite comparable dilation between the BA and DFA, the slope of the relationship between vessel diameter and shear rate was much greater in the arm (2.4 x 10(-4) +/- 4.6 x 10(-5) cm/s) than in either the DFA (8.9 x 10(-5) +/- 1.5 x 10(-5) cm/s) or CFA (2.1 x 10(-5) +/- 1.1 x 10(-5) cm/s). Together, these findings reveal a substantial heterogeneity in vascular responsiveness in the leg during dynamic exercise but demonstrate that conduit vessel dilation for a given change in shear rate is, nonetheless, reduced in the leg compared with the arm.     

Studies on the effects of the N-terminal domain antibodies of calcitonin receptor-like receptor and receptor activity-modifying protein 1 on calcitonin gene-related peptide-induced vasorelaxation in rat uterine artery

The vascular relaxation sensitivity to calcitonin gene-related peptide (CGRP) is enhanced during pregnancy, compared with nonpregnant human and rat uterine arteries. In the rat uterine artery, two types of CGRP receptors have been shown to coexist, CGRP-A receptor, which is a complex of calcitonin receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP(1)) and CGRP-B receptor, which is different from CRLR. In the present study, we hypothesized that: 1) CGRP-induced vasorelaxation in rat uterine artery is mediated through CGRP-A receptor and 2) N-terminal (Nt) domain of CRLR (Nt-CRLR) has a major contribution in ligand binding and mediating CGRP- induced relaxation effects in rat uterine artery. Polyclonal antibodies against Nt-domain of CRLR and RAMP(1) (Nt-RAMP(1)) were raised in rabbits and characterized for their specificity and were used to inhibit CGRP-induced vasorelaxation in rat uterine artery. For vascular relaxation studies, uterine arteries from Day 18 pregnant rats were isolated, and responsiveness of the vessels to CGRP was examined with a small vessel myograph. CGRP (10(-10) to 10(-7) M) produced a concentration-dependent relaxation of norepinephrine-induced contractions in Day 18 pregnant rat uterine arteries. These effects were significantly (P < 0.05) inhibited when uterine arteries were incubated with the antibody raised against Nt-CRLR (PD(2) = 6.75 +/- 0.20) and were totally abolished in presence of antibodies for both Nt-CRLR and Nt-RAMP(1) (PD(2) = 6.14 +/- 0.35). In contrast, a monoclonal antibody for CGRP-B receptor had no effect on CGRP-induced rat uterine artery relaxation. These studies suggest that CGRP effects in rat uterine artery are mediated through CGRP-A receptor and that Nt-domain of CRLR may play a predominant role in CGRP binding and thus in causing CGRP-induced uterine artery relaxation.     

Contraction of various zones of the rat testicular capsule in vitro induced by noradrenaline

The contractions induced by Noradrenaline (NA) on several preparations of the testicular capsule of the rat have been studied. Increasing concentrations of NA were added both in a single and cumulative way to the whole capsule and to some portions: the mediastinal and non mediastinal portions and to the anterior and posterior portions. All the preparations show concentration-dependent responses to NA except the non mediastinal portion. The maximal amplitude of the contraction was induced in the mediastinal portion, where the greatest amount of contractile cells exists. The NA dose that induces the maximal effect (Emax) is different in each preparation. A lower pD2 is obtained in the cumulative curves when they are compared with the non cumulative curves. In both concentration-response curves a desensitizing effect appears, when 3 X 10(-6)M of NA is reached in the cumulative ones and with higher NA doses in the non cumulative ones. Repeated single doses of NA (10(-5)M) also show desensitization. This effect is independent of the resting time between consecutive doses and it is not modified by propranolol (10(-6)M), normetanephrine (10(-5)M) or TMB-8 (10(-5)M), but it is decreased by imipramine (3 X 10(-8)M) and indomethacin (3 X 10(-6)M). This suggests that neural uptake and release of prostaglandins might be involved in this desensitization.     

Dietary manganese suppresses alpha1 adrenergic receptor-mediated vascular contraction

We examined the effect of dietary manganese (Mn) on the vascular contractile machinery in rat thoracic aortas. Weanling male Sprague-Dawley rats were fed either an Mn-deficient (MnD), Mn-adequate (MnA) or Mn-supplemented (MnS) diet (<1, 10-15 and 45-50 ppm Mn, respectively). After 15 weeks on the diets the rats were sacrificed and 3-mm aortic rings were contracted in six cumulative doses of the alpha(1) adrenergic receptor agonist L-phenylephrine (l-Phe, 10(-8) to 3 x 10(-6) M) under 1.5-g preload and relaxed with one dose of acetylcholine (3 x 10(-6) M) to assess intact endothelium. The maximal force (F(max)) of contraction and relaxation, as well as the vessel sensitivity (pD(2)) were determined. Manganese deficiency, assessed by hepatic Mn content, significantly lowered the rate of animal growth. A two-way analysis of variance revealed that MnS animals developed lower F(max) when contracted with L-Phe compared with the MnD and MnA animals (P相似文献   

Hemodynamic effects of corticotropin releasing hormone in the anesthetized cynomolgus monkey

Right atrial bolus administration of rat/human corticotropin releasing hormone (r/hCRH) at a dose of 90 micrograms/kg to anesthetized cynomolgus monkeys caused a dramatic and prolonged fall in both the peripheral vascular resistance (48% reduction) and mean systemic blood pressure (36% reduction). An associated tachycardia could be blocked with prior propranolol administration and thus was probably reflexic. A mean 43 and 37% increase in the flow of the superior mesenteric and common iliac arteries, respectively, was demonstrated with electromagnetic flow probes. These changes were associated with a concomitant 38 and 40% diminution in the respective vascular resistance. Similar blood flow changes were noted in the carotid artery, however, these were of a much shorter duration. None of these changes occurred in placebo-treated animals. Plasma adrenocorticotropic hormone and cortisol concentrations were elevated basally and throughout the procedure and were similar in the experimental and control groups, suggesting maximal activity of the hypothalamic-pituitary-adrenal axis. Plasma renin activity, however, gradually increased in the r/hCRH-treated animals, probably as a result of the systemic hypotension. We speculate that CRH or a CRH-like substance may function as a paracrine hormone modulating local blood vessel tone and may be important in directing blood flow during stress and injury. The vasoactive properties of exogenous r/hCRH may be of clinical use in man.     

Paradoxical effects of temperature on vascular tone

Temperature may have significant influence on vascular tone in such cases as organ preservation, coronary bypass surgery, and extracorporeal circulation. The aim of this research was to study the direct effect of temperature variation on vascular tone in an attempt to elucidate the mechanisms involved. In a first series of experiments, the isometric tension of two different vessels (rat thoracic aorta and pig renal branch artery) was studied at different temperatures. To study the role of calcium in this response, a second series of experiments was performed. In this the vessels were incubated with the intracellular chelator BAPTA/AM. Further experiments were performed to test the effect of cold storage. Our results show that changes in temperature lead to different results in pig renal artery and rat aorta. A decrease in temperature induced a highly reproducible relaxation in rat aorta, whereas pig renal artery presented cooling-induced contraction. Moreover, whereas calcium depletion failed to inhibit cooling-induced relaxation in rat aorta, it did not provoke cooling-induced contraction in pig renal artery. Similar responses were obtained with cold storage and calcium depletion. We intend to demonstrate that, just as the effect of temperature variation on pig renal artery is due to a metabolic mechanism, its effect on rat aorta may be due to structural factors. This hypothesis is supported by the result of histological studies which demonstrate a higher proportion of elastin fibres in rat aorta than in pig renal artery.     

The actions of leukotrienes C4 and D4 in the porcine renal vascular bed

The kidney of anaesthetised pigs was perfused in situ with carotid arterial blood. Renal blood flow and perfusion pressure were recorded. Close intra-arterial injection of leukotriene (LT) C4, D4 or noradrenaline (NA) caused a dose-related increase in vascular resistance. Both LTs were more active than NA by one to two orders of magnitude. Systemically-administered indomethacin potentiated the effect of all three agonists. Incubation of renal artery tissue with calcium ionophore A23187 in the presence of indomethacin resulted in the generation of LT-like material which, when assayed on guinea-pig ileum, was indistinguishable from LTD4. The results show that pig renal vessels produce LT-like material and suggest that the potent vasoconstriction induced by exogenous NA and LTs is modulated in vivo by a vasodilator cyclo-oxygenase product.     

Sex differences in vascular reactivity to adrenergic agents in the rat

• 1.1.The study was designed to determine if there are sex-dependent differences in vascular reactivity to adrenergic agents.
• 2.2.Vascular reactivity of both aortic and tail artery smooth muscle from male and female rats to various vasoactive agents was assessed. 3.li]The vascular response of aortic smooth muscle to both phenylephrine and isoproterenol were significantly greater in male rats as compared to females.
• 3.4.There were apparent sex differences in responsiveness to the KCl-induced, non-receptor mediated contraction of aortic smooth muscle in that the sensitivity to KCl was enhanced in male rats.
• 4.5.No sex differences were observed in tail artery preparations.
• 5.6.Phentolamine reduced the maximal tension induced by KCl in the tail artery but not aortic artery preparations. This effect was not sex dependent.
• 6.7.No differences in the vascular smooth muscle responsiveness to acetylcholine or sodium nitrate was observed between groups or within different vascular beds.
• 7.8.The increased sensitivity of males to adrenergic challenge could explain in part some of the existing sex differences in cardiovascular disease and hypertension.

     

Elevation of the vascular smooth muscle sensitivity to effects of constrictors after denervation and under decreased blood pressure

Changes in contractile activity of saphenous artery in normotensive rats and in rats with regional hypotension have been investigated. The abdominal aorta was partially occluded in Wistar rats distally to the renal arteries. Four weeks later, a 5-7-mm segment of the femoral nerve in one hindlimb was resected to denervate the saphenous artery. After two weeks, the isometric contraction of innervated and denervated saphenous artery segments was studied. In normotensive rats, the denervation augmented vessel sensitivity to noradrenaline, phenylephrine, serotonin, and KCl (in the presence of phentolamine). Chronic hypotension also augmented vessel sensitivity to constrictor agonists, whereas denervation did not result in further increase of sensitivity. In glyoxilic acid-stained preparations obtained from hypotensive rats, a reduced intensity of fluorescence of adrenergic fibers was observed. It was assumed that the higher sensitivity of vascular smooth muscle in hypotensive rats is due to functional disturbances of sympathetic innervation.     

Melatonin restores diminished neurogenic reactivity of the juvenile rat tail artery

The effect of melatonin on neurogenic reactivity of the juvenile rat tail artery segment was studied. The electrical field stimulation-evoked contraction of the segment decreased in the course of the experiment. Melatonin (0.1 microM) applied at different time points of the experiment produced an increase in the contraction, which directly correlated with a spontaneous decrease in the electrical field stimulation-evoked response. The increase in the potentiating effect of melatonin in the course of the experiment was not due to sensitization of the segment to this substance. Noradrenaline-evoked contraction of the vessel segment was not changed by melatonin. The data indicate that melatonin restores the diminished neurogenic reactivity of the juvenile rat tail artery probably by potentiation of the contractile response of the vessel, but this effect is hardly due to a change in sensitivity of the postjunctional membrane to noradrenaline.     

Chronic losartan treatment decreases angiotensin II-mediated facilitation of noradrenaline release in the caudal artery of spontaneously hypertensive rats

Sympathetic activity is modulated by angiotensin II (AII), both at pre- and postsynaptic level in the rat caudal artery. In the spontaneously hypertensive rat (SHR), this artery receives more dense sympathetic innervation than blood vessels of normotensive strains. This fact seems to be linked to the enhanced pressor responses elicited by noradrenaline in SHR. In this work we describe, in the SHR, the effect of a chronic treatment with the angiotensin II AT1-receptor antagonist, losartan, in modulating noradrenergic mechanisms involved in caudal artery contraction. The effect of losartan is compared to that of captopril, given at doses leading to a similar decrease of both arterial blood pressure and left ventricular hypertrophy. The contractile response of caudal artery rings induced by endogenous noradrenaline released by low frequency transmural nerve stimulation (TNS) has been studied. Under our conditions, TNS (0.5-1 Hz) induced higher contractile responses in SHR treated with losartan than in the control and captopril-treated groups. This difference seems to be due to an increase of the postsynaptic effect of noradrenaline (NA) rather than to an increase of noradrenaline release from sympathetic endings, since i) DE50 value for NA was lower in losartan-treated SHR than in the other groups, and ii) AII induced a dose-dependent increase of TNS-evoked release of radioactivity from caudal artery segments loaded with [3H]-NA, in both control and captopril-treated groups but had no effect in the losartan-treated group. These results show that chronic treatment with losartan, although slightly enhancing the pressor effect of NA at postsynaptic level, fully supresses the facilitatory role of AII on NA release.     

Functional Vascular Changes of the Kidney during Pregnancy in Animals: A Systematic Review and Meta-Analysis

Renal vascular responses to pregnancy have frequently been studied, by investigating renal vascular resistance (RVR), renal flow, glomerular filtration rate (GFR), and renal artery responses to stimuli. Nonetheless, several questions remain: 1. Which vasodilator pathways are activated and to what extent do they affect RVR, renal flow and GFR across species, strains and gestational ages, 2. Are these changes dependent on renal artery adaptation, 3. At which cellular level does pregnancy affect the involved pathways? In an attempt to answer the questions raised, we performed a systematic review and meta-analysis on animal data. We included 37 studies (116 responses). At mid-gestation, RVR and GFR change to a similar degree across species and strains, accompanied by variable change in renal flow. At least in rats, changes depend on NO activation. At late gestation, changes in RVR, renal flow and GFR vary between species and strains. In rats, these changes are effectuated by sympathetic stimulation. Overall, renal artery responsiveness to stimuli is unaffected by pregnancy, except for Sprague Dawley rats in which pregnancy enhances renal artery vascular compliance and reduces renal artery myogenic reactivity. Our meta-analysis shows that: 1. Pregnancy changes RVR, renal flow and GFR dependent on NO-activation and sympathetic de-activation, but adjustments are different among species, strains and gestational ages; 2. These changes do not depend on adaptation of renal artery responsiveness; 3. It remains unknown at which cellular level pregnancy affects the pathways. Our meta-analysis suggests that renal changes during pregnancy in animals are qualitatively similar, even in comparison to humans, but quantitatively different.     

Vasomotor effects of noradrenaline, acetylcholine, histamine, 5-hydroxytryptamine and bradykinin on snake (Trimeresurus flavoviridis) basilar arteries

We investigated the responsiveness of basilar arterial rings isolated from snakes to noradrenaline (NA), acetylcholine (ACh), histamine (His), 5-hydroxytryptamine (5-HT), mammalian bradykinin (BK) and rattlesnake BK. We also examined whether endothelial cells were involved in the responsiveness to ACh, BK, rattlesnake BK and in their resting vascular tone. NA and 5-HT induced concentration-dependent contractions. The cumulative concentration response curves of NA and 5-HT were shifted to the right in parallel by phentolamine (an alpha antagonist) and methiothepin (a 5-HT(1) and 5-HT(2) antagonist), respectively. However, ketanserin (a 5-HT(2) antagonist) had no effect on the cumulative concentration response curve of 5-HT. His, ACh, BK and rattlesnake BK had no effect on resting vascular tone; however, rattlesnake BK and sodium nitroprusside relaxed arteries precontracted by 5-HT. The rattlesnake BK-induced relaxations were almost abolished by L-nitro arginine (L-NA, a nitric oxide synthase inhibitor). L-NA and indomethacin (a cyclooxygenase inhibitor) had no effect on resting vascular tone or on precontracted arteries. These results suggest that alpha and 5-HT(1) receptor subtypes might be important in arterial contraction. Endothelial cells might play an important role in the responsiveness of snake basilar arteries to rattlesnake BK, but they might not be involved in the responsiveness to ACh, BK and in resting vascular tone.     

由左颈总动脉导管经肾动脉的大鼠肾脏无创伤给药法探讨

目的建立一种大鼠肾脏无创伤性局部血管给药的新方法,并对其给药后成活率和损伤性进行观察。方法 16只Wistar大鼠,用PE10导管经大鼠左侧颈总动脉-降主动脉-胸主动脉-腹主动脉,抵达肾动脉直接给药。统计其成活率并对给药的肾动脉血管行病理学观察。结果大鼠成活率可达87.5%,且不会造成肾动脉血栓或血管内皮损伤。结论该法可以成功的实现大鼠肾动脉远距离插管,零距离无创伤性局部血管给药,同时还可以推广用于腹腔的某些其它脏器甚至更远的后肢。     

Prominent contribution of L-type Ca2+ channels to cutaneous neurovascular transmission that is revealed after spinal cord injury augments vasoconstriction

In patients with spinal cord injury (SCI), somatosympathetic reflexes produce exaggerated decreases in skin blood flow below the lesion. This hypoperfusion appears to result from an increased responsiveness of cutaneous arterial vessels to neural activation. Here we investigated the mechanisms that underlie SCI-induced enhancement of neurovascular transmission in a cutaneous vessel, the rat tail artery. Isometric contractions of arterial segments from T11 spinal cord transected and sham-operated rats were compared 6 wk postoperatively. SCI more than doubled the amplitudes of contractions of arteries in response to moderate frequencies of nerve stimulation (0.1 to 1 Hz). In arteries from SCI rats, but not those from sham-operated rats, the L-type Ca(2+) channel blocker nifedipine (1 μM) reduced the amplitudes of nerve-evoked contractions. Furthermore, while the sensitivity to the agonists phenylephrine (α(1)-adrenoceptor selective) and clonidine (α(2)-adrenoceptor selective) did not differ significantly between arteries from SCI and sham-operated rats, nifedipine had a greater inhibitory effect on contractions to both agents in arteries from SCI rats. Although sensitivity to clonidine was unchanged, SCI selectively reduced the contribution of postjunctional α(2)-adenceptors to nerve-evoked contractions. In arteries from unoperated rats, the L-type channel agonist BAY K 8644 (0.1 μM) produced a similar enhancement of nerve-evoked contraction to that produced by SCI and also selectively reduced the contribution of α(2)-adrenceptors to these responses. Together the findings demonstrate that the SCI-induced enhancement of neurovascular transmission in the rat tail artery can largely be accounted for by an increased contribution of L-type Ca(2+) channels to activation of the vascular smooth muscle.     

A proposed role for prostaglandins in the modulation of the relaxation response to urotensin I in isolated rat arteries

Urotensin I (UI) elicits dose-dependent relaxation responses in isolated helical strips of rat tail and mesenteric arteries contracted by 10⁻⁵M norepinephrine (NE). The rat mesenteric artery demonstrated a 40 fold lower threshold sensitivity to UI (0.25 mU/M1 versus maximal relaxation at 0.25 mU/m1). Complete relaxation of the rat tail artery with UI could not be achieved, even at doses exceeding 10 mU/m1. Pretreatment of the arterial strips with cyclooxygenase inhibitors had no effect on the contractile response to NE in the tail artery, but reduced NE responsiveness in the mesenteric artery. Significant enhancement of UI relaxation responses in both types of arterial strips was achieved by pre-treatment with the cyclooxygenase inhibiters, suggesting a modulatory role for prostaglandins (PGs) in the expression of the UI relaxation response in NE contracted arterial strips. The major enzymatically formed PG (as assessed by [1-¹⁴C] PGH₂ metabolism in broken cell preparations) in both the rat tail and mesenteric arteries was 6-keto PGF_1α, the stable hydrolysis product of PGI₂. Using a specific RIA to quantify 6-keto PGF_1α release, it was found that UI elicited nearly a two-fold increase in the release of this PG compared to the NE control in both rat tail and mesenteric arteries. These data suggest that PGI₂ may modulate the relaxation response to UI either by direct physiological opposition (PGI₂ elicited contractile response in NE contracted tail and mesenteric arteries at doses exceeding 10−8M) and/or by some as yet undefined mechanism (eg. effects on Ca²⁺, cAMP).     

Effects of Renal Denervation on Renal Artery Function in Humans: Preliminary Study

Aim

To study the effects of RD on renal artery wall function non-invasively using magnetic resonance.

Methods and Results

32 patients undergoing RD were included. A 3.0 Tesla magnetic resonance of the renal arteries was performed before RD and after 6-month. We quantified the vessel sharpness of both renal arteries using a quantitative analysis tool (Soap-Bubble®). In 17 patients we assessed the maximal and minimal cross-sectional area of both arteries, peak velocity, mean flow, and renal artery distensibility. In a subset of patients wall shear stress was assessed with computational flow dynamics. Neither renal artery sharpness nor renal artery distensibility differed significantly. A significant increase in minimal and maximal areas (by 25.3%, p = 0.008, and 24.6%, p = 0.007, respectively), peak velocity (by 16.9%, p = 0.021), and mean flow (by 22.4%, p = 0.007) was observed after RD. Wall shear stress significantly decreased (by 25%, p = 0.029). These effects were observed in blood pressure responders and non-responders.

Conclusions

RD is not associated with adverse effects at renal artery level, and leads to an increase in cross-sectional areas, velocity and flow and a decrease in wall shear stress.     

Increased tail artery vascular responsiveness to angiotensin II in cold-treated rats

Chronic exposure of rats to cold for 1-3 weeks results in a mild form of hypertension. The renin-angiotensin system (RAS) has been implicated in this model of cold-induced hypertension. Previously we have characterized the vascular responsiveness in cold-acclimated animals, using aortic tissue, and recent studies have focused on the thermoregulatory responses of angiotensin II (AngII), utilizing the tail artery of the rat. Therefore in the current study we evaluated the vascular responsiveness of cold-treated rats to AngII in both aorta and tail artery at 2 and 4 weeks of cold exposure (5+/-2 degrees C). Systolic blood pressures were significantly elevated in cold-treated animals compared with control animals at both 2 and 4 weeks of cold exposure. At both of these time points body weights were reduced and ventricular weights were increased in cold-treated animals. After 2 weeks of cold exposure the vascular responsiveness of the aorta to AngII was significantly lower than that of controls. This vascular responsiveness to AngII was elevated and returned to control levels after 5 weeks of cold exposure. However, this pattern was not observed in the tail artery. The vascular responsiveness of tail artery rings from cold-treated rats to AngII was significantly greater than that of control animals during both 2 and 5 weeks of exposure to cold. The vascular contractile responses of both the aorta and tail artery to KCI in the cold-treated animals was not different from that of the control animals maintained at ambient room temperature, suggesting that the vascular smooth muscle contractile components were not altered by the cold exposure. Thus, the in vitro vascular reactivity to the receptor-mediated vasoconstrictor AngII was decreased in the sparsely innervated aorta and increased in the more densely innervated tail artery of the cold-treated animals when compared with controls. These results suggest that the increased responsiveness of AngII on the smooth muscle of the tail artery may play a role in adaptation to the cold and the maintenance of cold-induced hypertension.