Regional blood flows and resistances in conscious one-kidney, one-clip renovascular hypertensive rats

Three regional blood flows were measured in one-kidney, one-clip renovascular hypertensive (one-kidney hypertensive) rats with chronically implanted electromagnetic flow probe. One-kidney hypertensive rats showed about 30% greater superior mesenteric flow, about 20% greater hindquarter flow at the terminal aorta, and an almost unchanged renal flow at the clipped renal artery when compared with control rats, but the sum of the mean values of these three regional blood flows in one-kidney hypertensive rats was almost the same as that of control rats. One-kidney hypertensive rats had a higher peripheral resistance in all the investigated vascular areas. The increase in peripheral resistance of the renal area including the clipped and removed arteries was greater than that in peripheral resistance of the superior mesenteric area or hindquarter area. These findings suggest that the remaining renal area which failed to compensate for the flow deprived by uni-nephrectomy plays a role in the etiology of this kind of hypertension.     

Acute effects of captopril on blood pressure and regional blood flows in two types of renovascular hypertensive rats in conscious state

Mean arterial pressure and three regional blood flows--renal, superior mesenteric, and hindquarter flows--were monitored in conscious normotensive control rats (NCR), in two-kidney, one-clip (two-kidney), and in one-kidney, one-clip (one-kidney) hypertensive rats. After administering captopril, an angiotensin-converting enzyme inhibitor, mean arterial pressure decreased in all three groups. However, lowering of arterial pressure was not statistically significant in any of the groups. Renal flow increased significantly in the intact artery of two-kidney hypertensive rats, whereas it did not significantly increase in the clipped artery of one-kidney hypertensive rats and in the intact artery of NCR. Superior mesenteric flow increased significantly only in one-kidney hypertensive rats. Hindquarter flow did not significantly change in the three groups. Regional resistance reduced significantly in not only renal but also in superior mesenteric vascular area in two-kidney hypertensive rats, whereas it did not reduce significantly in these two vascular areas in one-kidney hypertensive rats and in NCR. The present findings show that the renin-angiotensin-mediated vasoconstriction plays a role in not only renal but also in superior mesenteric vascular area in two-kidney hypertensive rats, whereas it hardly plays a role in these three vascular beds in one-kidney hypertensive rats.     

Superior mesenteric sympathetic tone in conscious renovascular hypertensive rats

Blood flow in the superior mesenteric artery was observed with a chronically implanted electromagnetic flow probe in two-kidney, one-clip renovascular hypertensive rats (2K1C), one-kidney, one-clip renovascular hypertensive rats (1K1C), and normotensive control rats (NCR) in the conscious state. Arterial pressure was recorded with an indwelling catheter. Superior mesenteric resistance was calculated as arterial pressure divided by superior mesenteric flow. In all three groups of rats, superior mesenteric resistance remained almost unchanged when arterial pressure decreased markedly on ganglionic blockade with hexamethonium bromide. However, subsequent injection of a vasopressin antagonist (Manning compound) decreased superior mesenteric resistance significantly in 2K1C but not in 1K1C and NCR. Injection of vasopressin antagonist alone was without effect on arterial pressure and superior mesenteric flow in the three rat groups. Only 2K1C were judged to have appreciable sympathetic tone in resistance vessels of the superior mesenteric area, which was blocked by hexamethonium but compensated for by secondarily secreted vasopressin.     

Regional blood flow in conscious spontaneously hypertensive rats

In spontaneously hypertensive and normal control rats in the conscious state, blood flow was observed in the carotid artery, superior mesenteric artery, renal artery, and terminal aorta with a chronically implanted electromagnetic flow probe. At rest, flow per body weight was not different between the two groups except at the terminal aorta where it was significantly smaller in hypertensive rats (P less than 0.05). Regional peripheral resistance was higher in hypertensive rats than in normal rats in all the four arteries, but its elevation in the former was not uniform but most marked in the hindquarter area supplied by the terminal aorta. Quantitatively, this area was estimated to contribute about 40% of the total conductance decrease in hypertensive rats in comparison with the control. This suggests the importance of elevation of resistance in muscle blood vessels in hypertension. The contributions from the superior mesenteric area and the bilateral kidneys were estimated to be about 15% each. In the transposition response induced by transposing rats from their home cage to a new cage, the increase in hindquarter flow was significantly greater in hypertensive rats than in normal rats (P less than 0.01). The sum of the mean flows of the four arteries, a measure of cardiac output, was not different between hypertensive and normal rats at rest but greater in the former during transposition response. Elevation of arterial pressure in the response in hypertensive rats but not in the normal rats was ascribable largely to a greater increase in cardiac output in the former than the latter.     

Abnormal hindquarter vasoconstrictor tone, a feature common to various kinds of hypertensive rats

Hindquarter peripheral resistance, calculated as arterial pressure divided by hindquarter blood flow, decreased significantly on ganglionic blockade with hexamethonium bromide in four kinds of experimentally hypertensive rats, i.e. spontaneously hypertensive rats (SHR), DOCA-salt hypertensive rats, and one-kidney, one-clip and two-kidney, one-clip renovascular hypertensive rats, but not in normotensive control rats in the conscious state. Abnormal hindquarter vasoconstrictor tone seems to be a feature common to various kinds of hypertensive rats.     

Hemodynamic characteristics of conscious deoxycorticosterone acetate hypertensive rats

An electromagnetic flow probe was chronically implanted around the common carotid, superior mesenteric, or renal artery or the terminal aorta in deoxycorticosterone acetate (DOCA) hypertensive rats (prepared with DOCA and saline after uninephrectomy) and uninephrectomized control rats. A catheter for pressure measurement was inserted into the terminal aorta through a femoral artery. At rest the carotid and hindquarter (measured at the terminal aorta) blood flows in DOCA hypertensive rats were similar to the respective, corresponding values in normal rats with intact bilateral kidneys. The group mean of superior mesenteric flow was about 70% and that of renal flow about 40% larger than in normal rats. Cardiac output was estimated to be greater in DOCA hypertensive rats than in normal rats. In uninephrectomized control rats, superior mesenteric flow was larger than in normal rats to such an extent that an increase in cardiac output was assumed as in DOCA hypertensive rats, but renal flow was normal (about twice the unilateral renal flow in normal rats). Estimation of regional sympathetic vasoconstrictor tone from the decrease in peripheral resistance with hexamethonium and vasopressin antagonist revealed a substantial tone also in the superior mesenteric and hindquarter areas, where the tone was estimated to be almost absent in normal rats and uninephrectomized rats. It is suggested that hypertension in DOCA hypertensive rats is sustained by an increase in cardiac output and an elevation of vasoconstrictor tone in resistance vessels. Since increase in cardiac output appears to be similarly present in uninephrectomized control rats, the elevation of sympathetic tone due to administration of DOCA and salt seems to be indispensable for DOCA hypertension.     

Blood flow redistribution during spontaneous wheel walk of the rat

Changes in regional blood flow and arterial pressure in the rat during spontaneous walk in a wheel were observed. An electromagnetic flow probe was implanted around the carotid, superior mesenteric, or renal artery, or the terminal aorta and a catheter for pressure measurement was inserted into the terminal aorta or the common carotid artery. The wheel had a diameter of 35 cm and rotated passively as the rat walked. When hindquarter (terminal aortic) flow increased markedly during wheel walk, carotid flow decreased, superior mesenteric flow decreased or remained unchanged, and renal flow did not change. Arterial pressure remained almost unchanged and heart rate increased an average of about 10%. Semiquantitative considerations indicated that arterial pressure was maintained in the face of the profuse increase in hindquarter flow during wheel walk by an increase in cardiac output rather than shifts of blood flow from other regions.     

Mechanism of elevation of hindquarter vascular resistance in spontaneously hypertensive rats

In spontaneously hypertensive rats and normotensive control rats in the conscious state, hindquarter flow was observed with an electromagnetic flow probe chronically implanted around the terminal aorta. In separate groups of hypertensive and control rats, arterial pressure was observed with an indwelling catheter inserted into the terminal aorta. On ganglion blockade with hexamethonium bromide, hindquarter flow tended to increase in hypertensive rats and to decrease in normal rats. The percent change of hindquarter flow on ganglion blockade was significantly greater in the former than in the latter (p less than 0.05). Hindquarter peripheral resistance, estimated from flow and pressure values obtained in separate rat groups, was greater in hypertensive rats than in normal rats before ganglion blockade, but there was no difference between the groups after blockade. Presumably, an elevated sympathetic tone is responsible for the higher hindquarter peripheral resistance in spontaneously hypertensive rats, which plays an important part in the elevation of total peripheral resistance. However, bilateral lumbar sympathectomy did not induce chronic lowering of arterial pressure in hypertensive rats. This was at least partly due to the development of denervation supersensitivity.     

Regional difference in sympathetic vasoconstrictor tone in conscious rats

Regional differences in sympathetic vasoconstrictor tone were studied in conscious rats. In each rat an electromagnetic flow probe was chronically implanted around the common carotid, superior mesenteric, or renal artery, or the terminal aorta. An indwelling catheter for the measurement of arterial pressure was inserted into the terminal aorta via the right femoral artery. Peripheral resistance was calculated by dividing arterial pressure by flow. The per cent decrease in peripheral resistance on the ganglion blockade with hexamethonium bromide was used as a measure of regional sympathetic vasoconstrictor tone. A significant decrease in peripheral resistance, assumed to indicate a substantial tonic discharge to resistance vessels, was observed in conscious rats only in the carotid and renal areas and not in the superior mesenteric and hindquarter (supplied by the terminal aorta) areas. Since ganglion blockade also diminished the sum of the mean regional flows, cardiac output was estimated to decrease on the ganglion blockade. This suggests that capacitance vessels are also receiving a sizable vasoconstrictor tone, because the ganglion blockade did not elevate right atrial pressure. Pentobarbital anesthesia markedly inhibited the assumed tone to the renal area and was estimated to newly generate a tone to the hindquarters.     

Regional distribution of sympathetic vasoconstrictor tone in conscious spontaneously hypertensive rats

An electromagnetic flow probe was chronically implanted around the common carotid, superior mesenteric, or renal artery in spontaneously hypertensive rats (SHR). An indwelling catheter was inserted into the terminal aorta for measurement of arterial pressure. Peripheral resistance was calculated by dividing arterial pressure by flow. Decrease in peripheral resistance on ganglion blockade with hexa-methonium bromide was assumed to indicate the presence of vasoconstrictor tone to regional resistance vessels. In the conscious, resting state, peripheral resistance decreased significantly on ganglion blockade in the carotid and renal areas but not in the superior mesenteric area. The magnitudes of the decrease in peripheral resistance in the carotid and renal areas were not greater than the respective, corresponding values in normal rats. Presumably, vasoconstrictor tone in these three vascular regions, being quite different from that in the hindquarters, is not higher in SHR than in normal rats. Venomotor tone does not seem to be elevated in conscious SHR either, because the decrease in the sum of the mean peripheral flows on ganglion blockade, which was assumed to reflect the decrease in cardiac output, was not larger in SHR than in normal rats. Pentobarbital anesthesia did not abolish renal vasoconstrictor tone in SHR as it does in normal rats.     

Regional distribution of vasoconstrictor tone in acute spinal rats

Rats, chronically instrumented with an electromagnetic flow probe around the carotid, superior mesenteric, or renal artery, or the terminal aorta as well as having an arterial and venous catheter, were anesthetized with either and submitted to high spinal cord transection. One hour later, when the rats had recovered consciousness and the arterial pressure had recovered partially, hexamethonium was intravenously injected for ganglionic blockade. Peripheral resistance (arterial pressure/regional flow) was decreased significantly by ganglionic blockade in the carotid and renal areas but not in the superior mesenteric and hindquarter (terminal aortic) areas. This suggests the presence of sizable vasoconstrictor tone to resistance vessels in the carotid and renal areas but not in the superior mesenteric and hindquarter areas in the acute spinal rat. This distribution of vasoconstrictor tone is similar to that in intact conscious rats in the resting state and suggests the possibility that the vasoconstrictor tone for resistance vessels in intact rats is also for the most part generated in the spinal cord. Spinal transection decreased blood flow in all the four regions, suggesting a decrease in cardiac output due to dilation of capacitance vessels. It is possible that, in intact rats at rest, the so-called medullary vasomotor center is sending tonic impulses for the most part to capacitance vessels.     

Changes in cardiac output and peripheral flows on pentobarbital anesthesia in the rat

In rats chronically implanted with an electromagnetic flow probe around the ascending aorta, terminal aorta, or superior mesenteric artery as well as arterial and venous indwelling catheters, changes in cardiac output, hindquarter flow, splanchnic flow, and arterial pressure on pentobarbital anesthesia were observed. On intravenous injection of pentobarbital sodium at 30 mg/kg, arterial pressure dropped acutely from an average value of about 105 mmHg to a minimum of about 75 mmHg in about 5 min and then gradually recovered to an average level of about 90 mmHg in 30 min. Cardiac index gradually decreased about 30% on the average in 30 min. Hindquarter flow decreased about 25%. Superior mesenteric flow first increased about 40% within 5 min and then returned almost to the premedication level in 30 min. In adrenalectomized rats there was no decrease of hindquarter flow on pentobarbital anesthesia. The increase in superior mesenteric flow immediately after pentobarbital injection remained almost unchanged after adrenalectomy or splanchnicectomy. It is concluded that an appreciable portion of the decrease in cardiac output on pentobarbital anesthesia is induced by inhibition of tonic adrenomedullary secretion which has a dilating effect on muscle blood vessels through stimulation of beta-receptors. The marked increase in splanchnic flow immediately after pentobarbital injection, which is responsible for the concomitant drop in arterial pressure, is considered to be induced by a direct inhibitory effect of the anesthetic on splanchnic blood vessels.     

Redistribution of cardiac output during grooming of the rat

Changes in blood flow in the carotid, superior mesenteric, or renal artery or terminal aorta during grooming were measured in the conscious rat with a chronically implanted electromagnetic flow probe. Arterial pressure was measured simultaneously with an indwelling catheter. During grooming, carotid flow almost doubled and arterial pressure rose slightly, while hindquarter (terminal aortic) flow decreased by an average of about 20%. Superior mesenteric flow decreased occasionally and renal flow remained almost unchanged. Heart rate increased by an average of about 10%. An increase in carotid flow during grooming was similarly observed after cervical sympathectomy. After ganglion blockade with hexamethonium, grooming did not decrease hindquarter flow any more. These findings suggest that during grooming a substantial amount of blood flow is switched from the hindquarters to the carotid areas, to achieve a redistribution of cardiac output largely by excitation of the respective regional sympathetic and parasympathetic fibers and that sympathetic vasoconstrictor fibers supplying different vascular areas are controlled by separate pathways from separate neuron groups.     

Further evidence for abnormal hindquarter tone in spontaneously hypertensive rats

In spontaneously hypertensive rats (SHR) and normotensive control rats (NCR), hindquarter flow was observed in the conscious state with an electromagnetic flow probe chronically implanted around the terminal aorta. Arterial pressure was recorded with an indwelling catheter in the common carotid. When arginine vasopressin was infused intravenously at a rate of 12.5 ng/(kg.min), the increase in hindquarter resistance, calculated as arterial pressure divided by hindquarter flow, was significantly (p less than 0.005) augmented after ganglionic blockade with hexamethonium in SHR but not in NCR. This is explicable by assuming a tonic sympathetic vasoconstrictor activity in the hindquarters of SHR, reflexive inhibition of which partially offsets vasoconstrictor effect of infused vasopressin.     

Goldblatt hypertension and operant thermoregulation in shaved, sialoadenectomized rats

The thermobehavioral consequences of angiotensinogenic two-kidney (2K) and sodium-volume dependent one-kidney (1K) forms of Goldblatt (one-clip) renovascular hypertension were assessed in shaved, sialoadenectomized rats. The 2K group (n = 8) underwent unilateral renal artery stenosis with the contralateral kidney left intact; whereas the Sham-Operation (Sham-Op) Control group (n = 7) received only a laparotomy. The 1K group (n = 8) underwent unilateral renal artery stenosis with contralateral nephrectomy, and the Uninephrectomy Control group (n = 6) was only unilaterally nephrectomized. Shaping and testing was conducted in a convective thermal controller that permitted the experimenters to control, through continuously reinforced bar-pressing, the ambient temperature during exposure to warm (37 degrees C) or cold (17 degrees C) temperatures. Testing at each temperature occurred over two 6-hr sessions with an interpolated 48-hr rest period. Both 2K and 1K hypertensive rats exhibited longer durations of heat escape than their appropriate normotensive controls across both testing sessions. No differences were detected in response frequency, duration of cold escape responding, or body temperature. The results suggest that either the increased vascular resistance or the neuroendocrine-sympathetic disorder linked to the pathogenesis of Goldblatt renovascular hypertension may promote heat retention or lower heat tolerance.     

Sympathetic vasoconstrictor tone induced by pentobarbital anesthesia in hindquarters of rats.

Hindquarter (terminal aortic) blood flow (HQF) and arterial pressure (AP) were observed in rats with an electromagnetic flow probe implanted around the terminal aorta and an arterial indwelling cannula. Hindquarter peripheral resistance (HQR) was calculated by dividing mean AP by HQF. Under pentobarbital anesthesia, HQR was decreased significantly (p less than 0.001) by ganglionic blockade with hexamethonium bromide (C6). Since C6 does not change HQR significantly without anesthesia, we interpret that pentobarbital anesthesia generated a sympathetic vasoconstrictor tone in hindquarter resistance vessels. This was further substantiated by the observation that the increase in HQR on infusion of vasopressin was obscure under pentobarbital anesthesia: Presumably, the increase was offset by reflex inhibition of the hindquarter tone induced by anesthesia. The generation of hindquarter vasoconstrictor tone by pentobarbital was for the most part ascribable to the baroreceptor reflex to compensate for the depressor effect of this anesthetic, because it was greatly diminished after severance of the buffer nerves.     

“Structural autoregulation” of blood flow and GFR in the two renal vascular beds from two-kidney,one-clip renal hypertensive rats,as compared with kidneys from uni-nephrectomized and intact normotensive rats

Both kidneys from two-kidney, one-clip renal hypertensive rats (RHR) and the hypertrophied kidney of uni-nephrectomized rats (UNR) were investigated during artificial perfusion with 2% Dextran solution and kerosene at maximal vasodilatation, and studied with respect to organ weight, vascular resistance, preglomerular/postglomerular resistance ratio and glomerular filtration capacity. Paired perfusions were throughout used, isolated kidneys from age-matched normotensive rats serving as controls. The untouched, “high-pressure” RHR kidney had increased 40% in weight/100 g b. w. while its vascular resistance at maximal dilatation had increased almost 60%/g organ weight. Glomerular filtration capacity and preglomerular/postglomerular resistance ratio remained, however, largely unchanged.—The clipped “low-pressure”, RHR kidney was reduced 40% in weight and 45% in renal vascular resistance/g organ weight. It also showed a reduced pre/postglomerular resistance ratio and some reduction of filtration capacity.—The remaining hypertrophied kidney in UNR had increased 40% in weight, while its vascular resistance and filtration capacity/g organ weight, as well as its pre/postglomerular resistance ratio were unchanged. It is concluded that the kidney in renovascular hypertension rapidly adapts structurally not only in tissue mass, but also concerning total vascular resistance and pre/postglomerular resistance ratio, so as to chronically “autoregulate” GFR to match the altered pressure situation. Likewise, after unilateral nephrectomy the remaining, normotensive kidney increases in mass, with matched increases in blood flow and glomerular filtration capacity, while total resistance/g organ weight and the pre/postglomerular resistance ratio remain at normotensive levels.     

Central depressor effects of amino acids in conscious normotensive and two-kidney, one-clip renovascular hypertensive rats.

The circulatory effects of intracisternal injections of amino acids were investigated in conscious normotensive control rats (NCR) and in two-kidney, one-clip renovascular hypertensive rats (RHR). Arterial pressure was measured with an indwelling catheter connected to a pressure transducer. Heart rate was counted from the arterial pulse. The intracisternal injection of glycine, gamma-aminobutyric acid (GABA), taurine, serine, alanine, and sarcosine decreased blood pressure by an average of 16-30 mmHg in NCR and by an average of 32-55 mmHg in RHR. Both absolute and percent changes of depressor effects by GABA, taurine, serine, and alanine were larger in RHR than in NCR. All these amino acids also showed similar bradycardiac effects in both NCR and RHR, when compared in absolute values. The percent change of bradycardia induced by taurine and sarcosine was larger in RHR than in NCR. However, the degree of bradycardia by serine was larger in NCR than in RHR. These results suggest that serine, alanine, and sarcosine in addition to glycine, GABA, and taurine, play important roles in blood pressure control in conscious normotensive rats via central neural mechanisms and that the hypertension in renovascular hypertensive rats may involve a central abnormality.     

高血压大鼠大小动脉血管重构的差异比较

目的:探讨自发性高血压大鼠(SHR)大、小动脉血管重构的差异。方法:以20周龄雄性SHR为实验组,同龄Wistar-Kyoto(WKY)大鼠为对照组。每周测量体重和血压,43周龄大鼠麻醉取血,留取胸主动脉和肠系膜小动脉组织。HE染色观察比较大、小动脉形态学变化,天狼星红-维多利亚蓝染色检测胶原纤维和弹力纤维变化,激光扫描共聚焦显微镜和Western blot分析Ⅰ、Ⅲ型胶原蛋白的表达,透射电子显微镜观察动脉超微结构变化,原位末端标记法(TUNEL)和增殖细胞核抗原(PCNA)检测评估血管壁细胞凋亡与增殖情况。结果:小动脉血管内径(ID)和血管腔横截面积(LCSA)减小,壁厚内径比(WT/ID)和壁腔横截面积比(WCSA/LCSA)增大,外膜成纤维细胞增殖并部分迁移,胶原增多,以III型胶原增多为主,血管壁细胞的增殖指数和凋亡指数增加;主动脉ID、LCSA、WT/ID和WCSA/LCSA均增大,中层血管平滑肌细胞(VSMCs)肥大增生明显,胶原增多,血管壁细胞的增殖指数和凋亡指数增加。结论:高血压大鼠大、小动脉血管重构差异明显,小动脉以基质增多,特别是外膜III型胶原蛋白增多为主,血管壁细胞凋亡增加;大动脉以血管壁细胞增生,特别是VSMCs增生、肥大为主。     

半边莲生物碱缓解肾性高血压大鼠的血管重塑

目的： 探讨半边莲生物碱对肾性高血压大鼠主动脉血管重塑的影响。方法: 制备两肾一夹（2K1C）肾性高血压大鼠模型，灌服半边莲生物碱或卡托普利8周，用放射免疫技术测定血浆肾素活性（plasma rennin activity, PRA）。用Weigert法染色并测量腹主动脉中膜厚度及中膜截面积等血管重塑形态学参数。分别用Masson 三色法和免疫组化方法测腹主动脉总胶原蛋白含量和Ⅰ型胶原蛋白含量。结果: 高血压大鼠与假手术组相比PRA明显升高(P<0.05),使用半边莲生物碱后PRA显著降低(P<0.05);卡托普利对PRA无明显影响。高血压大鼠中膜厚度、中膜厚度/ 血管内径、中膜面积和腹主动脉胶原含量与假手术组相比明显升高(P<0.05)；半边莲和卡托普利均可使高血压组大鼠上述指标显著降低(P<0.05)。 结论: 肾性高血压大鼠存在血管重塑现象,半边莲生物碱能抑制胶原的表达、降低肾素活性,对缓解血管重塑有一定作用。