Myogenic properties of cerebral blood vessels from normotensive and hypertensive rats

1985 ◽  
Vol 249 (5) ◽  
pp. H914-H921 ◽  
Author(s):  
G. Osol ◽  
W. Halpern

Myogenic properties of posterior cerebral arteries from normotensive and hypertensive rats were analyzed in vitro and quantified in terms of both pressure range limits and degree of myogenic activity. Spontaneously hypertensive rat (SHR) vessels were significantly narrower in a fully relaxed state, and both wall thickness and wall-to-radius ratios were increased. After equilibration in 1.6 mM calcium physiological saline solution a substantial tone developed which resulted in average diameter decreases of 34 and 37% in Wistar-Kyoto (WKY) and SHR, respectively; average lumen diameters were approximately 125 micron. Rapid changes in transmural pressure (delta P 10-25 mmHg/s) were applied and diameter responses measured continuously. Myogenic responses began 1-3 s after a change in transmural pressure, and arteries regained their initial diameters after a pressure step in about 2 min; a final, steady-state diameter was achieved in 4-5 min. Myogenic pressure ranges were 49-145 mmHg in WKY and 64-181 in SHR; when responses were segregated according to positive and negative pressure steps, more myogenic responses were observed at lower pressures for pressure step decreases when compared with pressure step increases. Thus myogenic ranges for increasing pressure steps were 71-151 (WKY) and 72-188 mmHg (SHR) and for decreasing steps 45-117 (WKY) and 57-148 mmHg (SHR). Myogenic responses in SHR were weaker than in WKY rats: the former maintained essentially a constant diameter over a wide range of pressures, whereas arteries from the latter decreased diameter with increasing pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

1988 ◽  
Vol 254 (1) ◽  
pp. H28-H33 ◽  
Author(s):  
G. Osol ◽  
W. Halpern

Resistance-sized branches of posterior cerebral arteries from Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), spontaneously hypertensive stroke-prone (SHRSP), and antihypertensive-treated SHRSP (SHRSP-TRT) rats were studied in vitro. After the rats were killed, arterial segments were excised, mounted on microcannulas, and pressurized. After equilibration, intravascular pressure was increased in a stepwise fashion from 30 to 150-200 mmHg. All vessels developed a myogenic tone, which resulted in diameter reductions of 31-37% at 100 mmHg when compared with fully relaxed diameters [approximately 200 micron in 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid]. Differences in the extent of tone were not significant between animal groups (P greater than 0.05). Rhythmic vasomotion was present in 94% SHRSP and 100% SHRSP-TRT, 83% SHR, and only 6% of the WKY arteries. At higher pressures, the amplitude of the diameter oscillations decreased and frequency increased. Vasomotion was unaltered by tetrodotoxin or indomethacin, but could be abolished by cooling to 34 degrees C, ouabain (a depolarizing solution containing 125 mM K+), potassium-free physiological saline solution, or by calcium entry blockade with diltiazem or MnCl2. In normally quiescent WKY arteries, vasomotion, which was qualitatively similar to that observed in the hypertensive strains, could be induced by the addition of 5 mM tetraethylammonium chloride. Thus intrinsic oscillations in membrane calcium and potassium conductance may underlie the rhythmic contractile activity of rat cerebral arteries. This property appears to have a major genetic component, the expression of which is relatively independent of blood pressure history and is not related to the myogenic properties of the preparation.


2003 ◽  
Vol 285 (4) ◽  
pp. H1489-H1494 ◽  
Author(s):  
Ashley S. Izzard ◽  
Delyth Graham ◽  
Matthew P. Burnham ◽  
Egidius H. Heerkens ◽  
Anna F. Dominiczak ◽  
...  

The aims of the study were to compare the myogenic and structural properties of middle cerebral arteries (MCAs) from the stroke-prone spontaneously hypertensive rat (SHRSP) with MCAs from the spontaneously hypertensive rat (SHR) before stroke development in SHRSP. Rats were fed a “Japanese” diet (low-protein rat chow and 1% NaCl in drinking water) for 8 wk, and cerebral arteries were studied in vitro at 12 wk using a pressure arteriograph. Systolic pressure was significantly increased in SHRSP compared with SHR at 12 wk. Between 60 and 180 mmHg, MCAs from SHR maintained an essentially constant diameter, i.e., displayed a “myogenic range,” whereas the diameter of MCAs from SHRSP progressively increased as a function of pressure. Passive lumen diameter of MCAs from SHRSP was reduced at high pressure, and wall thickness and wall/lumen were increased, compared with SHR. Wall cross-sectional area was also increased in MCAs from SHRSP compared with the SHR, indicating growth. The stress-strain relationship was shifted to the left in MCAs from SHRSP, indicating decreased MCA distensibility compared with SHR. However, collagen staining with picrosirius red revealed a redistribution of collagen to the outer half of the MCA wall in SHRSP compared with SHR. These data demonstrate impaired myogenic properties in prestroke SHRSP compared with SHR, which may explain stroke development. The structural differences in MCAs from SHRSP compared with SHR were a consequence of both growth and a reduced distensibility.


1978 ◽  
Vol 235 (5) ◽  
pp. F409-F416 ◽  
Author(s):  
Gerald F. DiBona ◽  
Linda L. Rios

The mechanism of exaggerated diuresis and natriuresis was studied in spontaneously hypertensive rats (SHR) by renal clearance and micropuncture techniques. Control normotensive rats of the same age and sex [Wistar-Kyoto rats (WKY)] were also studied. During the hydropenic control and the volume-expansion experimental periods absolute and fractional water and sodium excretion were greater in SHR than in WKY. Although fractional and absolute water and sodium reabsorption were similar along the proximal convolution in SHR and WKY, fractional and absolute water reabsorption in Henle's loop was less in SHR than in WKY. Hydrostatic and colloid osmotic pressures in the cortical peritubular microvasculature were similar in WKY and SHR. Acute normalization of renal perfusion pressure by aortic constriction reversed the exaggerated diuresis and natriuresis in SHR by halving the filtered load of water and sodium; whole kidney and single nephron glomerular filtration rates and blood flows decreased by 50%. It is concluded that the exaggerated diuresis and natriuresis of the spontaneously hypertensive rat is caused by a decreased reabsorption in the loop of Henle. The mechanism of this decreased reabsorption in the loop of Henle cannot be explained by alterations in the measured physical forces in the renal cortical microvasculature. natriuresis; autoregulation; volume expansion Submitted on November 15, 1977 Accepted on June 7, 1978


1981 ◽  
Vol 61 (s7) ◽  
pp. 219s-221s ◽  
Author(s):  
J. P. Chalmers ◽  
P. R. C. Howe ◽  
Y. Wallmann ◽  
I. Tumuls

1. We have studied the number of phenylethanolamine-N-methyltransferase (PNMT)-containing nerve cells in the medulla and the activity of PNMT in the medulla, spinal cord and hypothalamus of the rat. 2. At 4 weeks of age there was an increase in the number of PNMT cells counted in the medulla of the spontaneously hypertensive rat (SHR; 21%, P < 0.01) and the stroke-prone spontaneously hypertensive rat (SHR-SP; 22%, P < 0.01) compared with the Wistar-Kyoto (WKY) control rat. 3. At 4 months of age there were no significant differences in the number of medullary PNMT cells in two normotensive strains (WKY and Fisher rats), two genetically hypertensive strains (SHR and SHR-SP) and in DOCA-salt hypertensive rats. 4. In four week old rats the activity of PNMT was increased by about 50% in the spinal cord and medulla of the SHR and SHR-SP compared with the WKY rats, and immunotitration experiments suggest that this is due to an increased concentration of enzyme. 5. At 4 months of age there were no increases in PNMT activity of either genetically hypertensive rats or DOCA-salt hypertensive rats.


1986 ◽  
Vol 250 (4) ◽  
pp. G412-G419
Author(s):  
H. P. Schedl ◽  
D. L. Miller ◽  
R. L. Horst ◽  
H. D. Wilson ◽  
K. Natarajan ◽  
...  

We previously found intestinal Ca2+ transport to be lower in the spontaneously hypertensive (SH) as compared with the Wistar-Kyoto control (WKY) rat. These animals were fed a relatively high (1%) Ca2+ diet, and the concentration of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] in serum was the same in both groups. In the present experiment we tested the possibility that the lower Ca2+ transport in the SH rat was the result of unresponsiveness to 1 alpha,25(OH)2D3. We fed diets high and low in Ca2+ and measured serum 1 alpha,25(OH)2D3 and Ca2+ transport. Serum 1 alpha,25(OH)2D3 increased in response to Ca2+ depletion at both 5 and 12 wk in both the WKY and SH rat. With high-Ca2+ diet, Ca2+ transport was lower in SH than in WKY when studied 1) in vitro in duodenum at 5 wk of age, and 2) in vivo in proximal and distal small intestine at 12 wk of age. Ca2+ transport increased in SH in response to Ca2+ depletion, but not in WKY, except in distal small intestine in vivo at 12 wk. In summary, although Ca2+ transport is lower in the SH as compared with the WKY rat when vitamin D activity is basal through feeding a high-Ca2+ diet, Ca2+ transport increases in the SH rat in response to the increase in 1 alpha,25(OH)2D3 produced by feeding a low-Ca2+ diet. We conclude that 1) the vitamin D-regulated component of mediated Ca2+ transport is intact in the SH rat and is unrelated to hypertension, and 2) mediated Ca2+ transport under basal conditions, i.e., nonvitamin D-regulated, differs in the SH and WKY rats and may be related to hypertension.


1986 ◽  
Vol 251 (2) ◽  
pp. F278-F282 ◽  
Author(s):  
U. Gafter ◽  
S. Kathpalia ◽  
D. Zikos ◽  
K. Lau

Calcium absorption by spontaneously hypertensive rats (SHR) was variably reported to be different from normotensive Wistar-Kyoto (WKY) controls. Furthermore, blunted responsiveness to the intestinal effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has also been postulated. To evaluate this hypothesis, calcium fluxes were measured by the Ussing technique across duodenum and descending colon with or without prior 1,25(OH)2D3 treatment. Duodenal mucosal-to-serosal calcium flux (Jm----s) (44.9 vs. 52.4 nmol X cm-2 X h-1), serosal-to-mucosal flux (Js----m) (25.6 vs. 28.4 nmol X cm-2 X h-1), and net flux (Jnet) were comparable. 1,25(OH)2D3 increased duodenal Jm----s in both SHR and WKY groups (95.2 and 86.8 nmol X cm-2 X h-1). Js----m was lower in SHR (26.1 vs. 35.6 nmol X cm-2 X h-1, P less than 0.01), although the tendency for a higher Jnet in SHR (68.6 vs. 51.2 nmoles X cm-2 X h-1) was statistically insignificant. Short-circuit current was higher in the colon of SHR, both before and after 1,25(OH)2D3, suggesting increased sodium transport. Basal colonic Jnet was virtually zero in both groups but comparably increased by 1,25(OH)2D3 because of stimulation in only Jm----s. Prevention of hypertension by hydralazine since the 4th wk of age did not alter the findings compared with the hypertensive SHR, suggesting calcium transport rates were unaffected by hypertension. These data indicate that in vitro, duodenal, and colonic active calcium transport by the SHR is similar to WKY. Their normal responses to 1,25(OH)2D3 do not support the hypothesis of intestinal resistance.


1996 ◽  
Vol 270 (1) ◽  
pp. H1-H6 ◽  
Author(s):  
A. S. Izzard ◽  
S. J. Bund ◽  
A. M. Heagerty

To investigate myogenic tone during the developmental and established phases of hypertension, segments of distal (6th order) mesenteric arteries from spontaneously hypertensive rats (SHR) at 5 and 20 wk were isolated and pressurized in vitro and compared with vessels from age-matched Wistar-Kyoto (WKY) control animals. At 5 wk, tone was significantly enhanced in the SHR. At 20 wk tone was no longer significantly increased over a wide pressure range, although arteries from the SHR were able to maintain diameter at all pressures studied, whereas vessels from the WKY exhibited forced distension at 180 and 200 mmHg. From the relative slope of the pressure-diameter relationship (myogenic index), no increase in peak myogenic responsiveness was observed in arteries from the SHR at either time point. Passive lumen diameters were significantly decreased in arteries from SHR at both time points. From the total and passive midwall circumference-tension relationships, total tension was observed at a reduced midwall circumference in the SHR, but increased absolute levels of total tension were not observed. The normalized midwall circumference-tension relationships in the two strains revealed increased total tension due to active tension development at a reduced normalized circumference at 5 wk in the SHR. At 20 wk the normalized midwall circumference-tension relationships in the two strains were identical. These results demonstrate that myogenic tone in mesenteric arteries is enhanced during the development of hypertension but not when it is established, except at high intraluminal pressures.


1994 ◽  
Vol 266 (3) ◽  
pp. H1027-H1033 ◽  
Author(s):  
M. A. Hajdu ◽  
G. L. Baumbach

The goal of this study was to investigate factors that contribute to reductions in internal diameter of large and small cerebral arteries during chronic hypertension. We measured diameter of second- and third-order branches of the posterior cerebral artery in vitro during maximal dilation with EDTA in 6-mo-old stroke-prone spontaneously hypertensive rats (SHRSP, n = 7) and Wistar-Kyoto rats (WKY, n = 7). Cross-sectional area of the vessel wall, measured histologically, was not significantly different at 70 mmHg in SHRSP and WKY in large or small branches of posterior cerebral artery. In large branches of posterior cerebral artery, external and internal diameters were significantly less at 70 mmHg in SHRSP than in WKY, whereas external and internal diameters converged at 0 mmHg in the two groups of rats. In small branches, on the other hand, external and internal diameters were significantly less at all levels of intravascular pressure in SHRSP than in WKY. The stress-strain relation in posterior cerebral artery of SHRSP was shifted to the left in large branches and to the right in small branches, which indicates that distensibility was reduced in large cerebral arteries of SHRSP and increased in small cerebral arteries. These findings suggest that different mechanisms are responsible for impairment of maximal dilator capacity in large and small cerebral arteries of SHRSP: reduced distensibility in large arteries and remodeling with reduced external diameter in small arteries. Furthermore the findings provide additional support for the concept that hypertrophy may not be a primary factor in impaired maximal dilation.


1994 ◽  
Vol 72 (10) ◽  
pp. 1208-1214 ◽  
Author(s):  
Shannon L. Venance ◽  
Brian M. Bennett ◽  
Stephen C. Pang

Understanding the mechanism behind the growth response evident in the vasculature of the spontaneously hypertensive rat (SHR) remains elusive. Fibroblasts from the aortic adventitial layer of the SHR manifest the heightened proliferative rate in vitro relative to Wistar–Kyoto (WKY) rats that is conspicuous in cultured aortic smooth muscle cells. The adenylyl-cyclase/cyclic AMP signal transduction pathway is believed to be altered in hypertensive people and animals such that responses to β-adrenoceptor activation are blunted. The present study examined the effects of β-adrenoceptor-mediated versus direct activation of adenylylcyclase on intracellular cyclic AMP accumulation and subsequent DNA synthesis in cultured aortic fibroblasts. We hypothesized that elevation of cyclic AMP levels by both isoproterenol and forskolin would normalize the proliferative capacity of SHR fibroblasts. Forskolin increased intracellular cyclic AMP levels and inhibited epidermal growth factor stimulated thymidine incorporation in an equivalent manner in both SHR and WKY adventitial fibroblasts, implying that there is no difference in adenylylcyclase activity. Isoproterenol elevated cyclic AMP levels to a significantly greater degree in the SHR than did forskolin, and yet, relative to forskolin, attenuated growth factor induced DNA synthesis to a lesser extent. These data suggest that isoproterenol, via β-adrenoceptor activation, exhibits both cyclic AMP dependent and cyclic AMP independent effects in adventitial fibroblasts. The cyclic AMP independent effects of isoproterenol oppose the expected observations due to cyclic AMP and may offer an explanation to the blunted responses to β-adrenoceptor activation evident both in vitro and in vivo.Key words: spontaneously hypertensive rats, cultured adventitial fibroblasts, aorta, isoproterenol, forskolin, DNA synthesis, cyclic AMP.


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