Differences of cardiac reactivity between spontaneously hypertensive and normotensive rats

Fujiwara, M.; Kuchii, Masato; Shibata, Shoji

doi:10.1016/0014-2999(72)90070-2

Cited by 54 publications

(13 citation statements)

References 6 publications

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“…This is especially true since cAMP has been shown to be closely associated with vascular smooth muscle relaxation (8). Similar subsensitivity of AC activity from the hearts of the hypertensive animals may explain the decreased ability of the hearts from these animals to synthesize cAMP (20) and to react normally to ,Badrenergic stimulants (21).…”

Section: Discussionmentioning

confidence: 97%

Aberrations of Cyclic Nucleotide Metabolism in the Hearts and Vessels of Hypertensive Rats

et al. 1974

Proc. Natl. Acad. Sci. U.S.A.

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In the aortas and mesenteric arteries from spontaneous hypertensive rats and in the aortas from stress-and desoxycorticosterone-acetate-hypertensive rats, the intracellular cGMP: cAMP ratios were significantly elevated when compared to the ratios in the aortas of the respective controls. Decreases in the intracellular cAMP or cGMP levels were consistently associated with increased activity of the cyclic-nucleotide-specific low Km phosphodiesterase (3': 5'. Previous studies from this laboratory have indicated that the aortas from spontaneous and stress hypertensive rats (1) and more recently from neurogenically hypertensive rats (2) contained lesser amounts of 3': 5'-cAMP due primarily to increased rates of hydrolysis of the cyclic nucleotide. The decrease in the intracellular levels of cAMP was proposed as a possible mechanism for the increased vascular resistance and the vascular smooth muscle changes associated with the three rat models of hypertension.In the present work, studies were conducted with tissues from rats made hypertensive by combined desoxycorticosterone acetate (DOCA) and salt administration. The role of 3': 5'-cGMP, the other naturally occurring cyclic nucleotide, which is now being considered as an important partner for cAMP in the control of cellular function (3-5), was also investigated. MATERIALS AND METHODSSpontaneous and stress hypertensive rats and their respective controls were obtained as previously described (1). DOCAhypertensive rats were prepared as described by Stanton and White (6). Systolic blood pressures were determined indirectly by the tail cuff technique and were 192 ± 3, 165 + 4, and 226 + 1 mm Hg for the spontaneous, stress, and DOCA-hypertensive rats, respectively. Control rats for those same groups had pressures of 130 + 2, 125 A 2, and 132 4 2 mm Hg, respectively. Values are i SEM.Most of the experiments were carried out on the aortas, mesenteric arteries, and hearts removed from the animals immediately after their decapitation. A portion of each tissue (20-30 mg) was immediately frozen in liquid nitrogen and kept frozen at -20°until analyzed for cyclic nucleotide contents within 2 weeks. The remainder of the fresh tissue was homogenized in 4 volumes of ice-cold isotonic sucrose, kept at 40, and assayed for pertinent enzyme activities within 2 hr.The aortas and mesenteric arteries from two to four animals were combined into each sample. cAMP and cGMP levels and phosphodiesterase (PDE, 3': 5'-cAMP 5'-nucleotidohydrolase, EC 3.1.4.17) adenylyl cyclase [AC, ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and guanylyl cyclase [GC, GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activities were determined as described previously (1,7). The cyclic nucleotide index was calculated according to the formula: cAMP content in control cAMP content in hypertensive cGMP content in control cGMP content in hypertensive RESULTSIn the spontaneously hypertensive rat the aortas contained significantly less cAMP and more cGMP than did the control aortas (Table 1). Aortas of stress ...

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Section: Discussionmentioning

confidence: 97%

Aberrations of Cyclic Nucleotide Metabolism in the Hearts and Vessels of Hypertensive Rats

et al. 1974

Proc. Natl. Acad. Sci. U.S.A.

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“…Impaired sympathetic control of cardiac performance has been shown in experimental hypertension (2,14,32). Recently Saragoca and Tarazi (36) have demonstrated reduced inotropic response to isoproterenol stimulation in SHR hearts.…”

Section: Introductionmentioning

confidence: 97%

Reduced cAMP levels and glycogen phosphorylase activation in isoproterenol perfused SHR myocardium

et al. 1983

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The effect of isoproterenol perfusion on cAMP levels and phosphorylase activity was investigated in the spontaneously hypertensive rat (SHR) and Kyoto Wistar normotensive control rat (WKY) heart. The basal force of contraction in physiological salt solution perfused hearts was comparable between SHR and WKY. However, the force of contraction in response to 10 nM isoproterenol perfusion was decreased approximately 20-30% in SHR heart as compared to WKY heart. Basal cAMP levels were reduced in SHR hearts as compared to WKY hearts. Isoproterenol perfusion resulted in an increase in cAMP levels over the basal cAMP values which was 50% and 100% in SHR and WKY hearts, respectively. Basal phosphorylase activity was higher in SHR hearts as compared to WKY hearts. However, the percentage increase in phosphorylase activity by isoproterenol perfusion over the basal values was approximately 400% in WKY hearts and only 200% in SHR hearts. The ouabain-sensitive (Na+, K+)-ATPase activity, Ca2+ binding in the absence of ATP, sialic acid content, and 5'-nucleotidase activity of purified cardiac plasma membranes was not altered in SHR as compared to WKY. These results would suggest beta-adrenergic mediated adenylate cyclase stimulation is decreased in SHR myocardium while other plasma membrane properties and associated enzymes may not be altered.

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“…Hearts of animals with experimentally induced hypertension have a decreased sensitivity to catecholamines (Cohen and Berkowitz, 1976;Fuyiwara et al, 1972;Kunos et al, 1978). Moreover, in vitro experiments have shown that membrane fractions prepared from hypertensive hearts have a decreased catecholamine-stimulated adenylate cyclase activity (Amer, 1973;Amer et al, 1975).…”

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confidence: 99%

Decreased cardiac beta-adrenergic receptors in deoxycorticosterone-salt and renal hypertensive rats.

Woodcock¹,

Funder²,

Johnston³

1979

Circulation Research

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SUMMARY The development of experimental deoxycorticosterone-salt (DOCA-salt) and renal artery clip hypertension in rats is associated with alterations in the sensitivity of the myocardium to adrenergic stimulation. We studied /3-adrenergic receptors and isoproterenol-stimulated adenylate cyclase in myocardial membranes from hypertensive rats to determine whether this altered sensitivity is associated with any change in /3-adrenergic receptors. The specific binding of the /J-adrenergic antagonist, '"I-iodohydroiybenzylpindoloL, was used to measure numbers and affinities of receptors in myocardial membrane preparations. Cardiac membranes from both DOCA-salt and renal hypertensive rats showed significantly fewer /3-receptors than did membranes from control, normotensive rats. Receptor affinity remained unchanged. This decrease was from 110 ± 19 to 49 ± 5 fmol/mg protein for DOCA-salt hypertension and from 110 ± 18 to 75 ± 16 fmol/mg protein for renal artery clip hypertension. Isoproterenol-stimulated adenylate cyclase activity also was lower in membranes from hypertensive rats, whereas basal and fluoride-stimulated activities were unchanged. drc Res 45: 560-565, 1979 THE quantitative importance of the sympathetic nervous system in relation to normal blood pressure control and to the etiology of various types of hypertension still is uncertain. However, several observations have suggested changes in sympathetic activity in essential hypertension and in various experimental hypertensive models. Elevated plasma catecholamine levels are found in a proportion of hypertensive patients (de Champlain, 1977), and many commonly used antihypertensive drugs interfere with the function of some part of the sympathetic nervous system. In experimental deoxycorticosterone-salt (DOCA-salt) and in renal hypertension, plasma catecholamines also are elevated (de Champlain, 1977;Reid et al., 1977). Moreover, destruction of the sympathetic nervous system with 6-hydroxydopamine and adrenalectomy prevents the establishment of hypertension in these animal models (Chalmers, 1975). Changes in sympathetic activity in experimental hypertension also have been shown by alterations in the turnover of norepinephrine, a decreased turnover being reported in the brain stem and an increased turnover in the heart (de Champlain, 1977). Presumably, this implies increased cardiac sympathetic drive in these models. This increased sympathetic drive, together with the reduced ability for norepinephrine uptake reported for DOCA-salt hypertension (de Cham-

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Differences of cardiac reactivity between spontaneously hypertensive and normotensive rats

Cited by 54 publications

References 6 publications

Aberrations of Cyclic Nucleotide Metabolism in the Hearts and Vessels of Hypertensive Rats

Aberrations of Cyclic Nucleotide Metabolism in the Hearts and Vessels of Hypertensive Rats

Reduced cAMP levels and glycogen phosphorylase activation in isoproterenol perfused SHR myocardium

Decreased cardiac beta-adrenergic receptors in deoxycorticosterone-salt and renal hypertensive rats.

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