Participation of Neural Factor in the Pathogenesis of Hypertension in the Spontaneously Hypertensive Rat

SUMMARYCardiac output of unanesthetized spontaneously hypertensive rats (SHR) and normotensive control rats (NCR) was measured by an aortic pressure pulse contour method. A catheter was introduced into the aortic arch under ether anesthesia and aortic pressure curves were recorded after the recovery from anesthesia. Stroke volume was calculated by reading required pressure and time data on the tracings and substituting them into a special equation. Cardiac output per min per body weight was not significantly different between SHR and NCR. Arterial pressure and total peripheral resistance were higher in SHR than in NCR. On ganglion blockade with hexamethonium bromide in the conscious state, arterial pressure decreased more markedly in SHR than in NCR. Though arterial pressure was still significantly (P< 0.05) higher in SHR after blockade, cardiac output was larger in SHR more than to account for the difference in arterial pressure. Total peripheral resistance was lower in SHR than in NCR after blockade. It is concluded that, even in the conscious state as in the anesthetized state, the major contribution to the hypertensive state in SHR is an increase in total peripheral resistance due to an elevation of the sympathetic tone.Additional Indexing Words: SHR Sympathetic hypertension Ganglion blockade Cardiac output Aortic compliance CUTE experiments on anesthetized spontaneously hypertensive rat or SHR (Okamoto and Aoki1)) have indicated that the hypertensive state is principally ascribable to an increase in total peripheral resistance due to an elevation of the sympathetic tone.2)-5) However, the question still remains unsettled as to whether this also holds for the unanesthetized, conscious state. Therefore, in the present study, aortic pressure was recorded in conscious SHR and control Wistar rats and cardiac output was calculated by a pulse contour method. This and other hemodynamic parameters were compared

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“…which is a rearrangement of equation (2). P1, P2, Ps, and Ts are to be read from the simultaneous tracing of aortic pressure.…”

Section: Methodsmentioning

confidence: 99%

Hemodynarnics of Spontaneously Hypertensive Rats in Conscious State

1975

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“…Though the hypertension develops in the early stage without certain etiology, the animals in the advanced stage exhibit the vascular lesions such as periarteritis nodosa, nephrosclerosis and cardiac lesions (2-5). Recently, Okamoto et al (6,7) and Matsumoto (8) have indicated further some involvement of neural factors in development and maintenance of the hypertension.In order to elucidate pharmacologically the mode of the hypertension in the SH rats, the depressor responses to the anti-hypertensive agents were observed comparatively be tween in the SH and normotensive (N) rats. …”

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confidence: 99%

Depressor Responses of the Spontaneously Hypertensive Rats to the Anti-Hypertensive Agents

Nagaoka

Kikuchi

Aramaki

1969

Japanese Journal of Pharmacology

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A variety of experimental hypertensions in rats has been available for the evaluation of the anti-hypertensive agents as well as for the mechanism studies of essential hyperten sion. The spontaneously hypertensive (SH) rat with 100 per cent incidence of heredity has been separated from the Wistar rats (1). Though the hypertension develops in the early stage without certain etiology, the animals in the advanced stage exhibit the vascular lesions such as periarteritis nodosa, nephrosclerosis and cardiac lesions (2-5). Recently, Okamoto et al. (6,7) and Matsumoto (8) have indicated further some involvement of neural factors in development and maintenance of the hypertension.In order to elucidate pharmacologically the mode of the hypertension in the SH rats, the depressor responses to the anti-hypertensive agents were observed comparatively be tween in the SH and normotensive (N) rats. MATERIALS AND METHODSFor the establishment of a dose-response relationship of the anti-hypertensive agents, specific pathogen free SH* (F13,14) and N rats of 17 to 25 weeks of age were used as a group of 5 rats per one dose level of each drug. The daily administrations of the following drugs in the conventional SH and N rats were as follows: 19 female SH rats (F,,,,,) of 6 and 15 weeks of age for hydrochlorothiazide, 8 SH and 8 N rats of 10 and 19 weeks of age for cmethyl DOPA and 18 SH and 18 N rats (7 to 12 months of age) for hydralazine, reserpine and guanethidine. The animals were kept in a room at a temperature of 23 to 24°C and fed stock diet and tap water ad libitum.Systolic blood pressure was determined in unanesthetized animals using Nakao et al.'s tail cuff method (9). Heart rate was calculated from the amplified pulse waves being taken during the blood pressure measurement. The measurements were carried out at one hour before and at 1, 4, 7 or 8, 24 and 48 hours after drug administration. Prior to the administration, the animals in our experiments were accustomed to the measurement handling 2 or 3 times in the preceding week.* Production of specific pathogen free animals were carried out by us in the spontaneously hypertensive and normotensive rats.

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“…33 Heightened tonic sympathetic activity of central origin has been implicated as a major contributing factor in the initiation and maintenance of elevated blood pressure in SHR. 38 The RVLM is a major integration site for sympathetic nervous activity in the central nervous system and is involved in tonic and reflex control of arterial pressure. 39 This vasomotor area receives input from the nucleus of the solitary tract, the major site of termination of baroreceptor and cardiopulmonary afferent neurons, and neurons originating in this area project directly to the intermediolateral cell columns of the thoracic spinal cord where they innervate preganglionic sympathetic neurons.…”

Section: Discussionmentioning

confidence: 99%

Rostral ventrolateral medulla as a site for the central hypertensive action of kinins.

1994

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In the present study, we focused on the rostral ventrolateral medulla as a possible site of action for kinins because of its established importance in the central regulation of the cardiovascular system. Unilateral microinjections of 100 pmol to 4 nmol bradykinin into the rostral ventrolateral medulla produced dose-dependent increases in mean arterial pressure in Sprague-Dawley (SD) rats, Wistar-Kyoto (WKY) rats, and spontaneously hypertensive rats (SHR). The doseresponse curves for the hypertensive responses to bradykinin in SD and WKY rats were essentially the same, whereas the hypertensive effect of bradykinin was significantly greater in SHR than in either SD or WKY rats. -bradykinin produced prolonged dose-dependent decreases in mean arterial pressure and heart rate. Blood pressure decreased 70±8 mm Hg and heart rate decreased 49±9 beats per minute in SHR, whereas in WKY rats mean arterial pressure decreased 12±4 mm Hg, with no change in heart rate. In a similar fashion, Hoe 140 caused a 51±7 and 17±3 mm Hg reduction in blood pressure in SHR and WKY rats, respectively. Collectively, these results suggest that a hyperactive kallikrein-kinin system in this region of the brain may be involved in the maintenance of blood pressure in the SHR model. (Hypertension. 1994^3:52-58.)Key Words • kallikrein-kinin system • central nervous system • blood pressure I ncreasing evidence suggests the presence of an endogenous tissue kallikrein-kinin system within the brain. A tissue kallikrein indistinguishable from rat urinary kallikrein has been isolated and characterized in rat brain, and its synthesis is directed in cell-free translation systems by brain mRNA.1 Tissue kallikrein has been localized immunocytochemically in hypothalamic cell bodies and brain ventricular epithelium 2 and quantitated in several other sites by radioimmunoassay techniques.3 Bradykinin-immunoreactive neuronal systems also have been localized immunocytochemically within the brain, 4 and bradykinin has been found in mammalian brain tissue. 5 In addition, the presence of immunoreactive kinin in canine 6 and rat 7cerebrospinal fluid also has been demonstrated. Kininogen has been detected in human cerebrospinal fluid 8 and recently has been localized immunohistochemically in neurons of the hypothalamus of the adult rat. 9 Lastly, the cDNA for the rat bradykinin B2 receptor was recently reported, and an mRNA encoding the bradykinin B2 receptor was found to be present in the rat brain. 10The function or functions of the brain kallikrein-kinin system remain to be defined, although a role for kinins in central cardiovascular regulation has been suggested by pharmacologic studies in which the administration of bradykinin into the central nervous system caused inReceived January 14,1992; accepted in revised form September 16, 1993. From the Department of Pharmacology, Medical University of South Carolina, Charleston.Correspondence to Philip J. Privitera, PhD, Department of Pharmacology, Medical University of South Carolina, 171 Ashley Ave, Charle...

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Participation of Neural Factor in the Pathogenesis of Hypertension in the Spontaneously Hypertensive Rat

Cited by 208 publications

References 2 publications

Hemodynarnics of Spontaneously Hypertensive Rats in Conscious State

Hemodynarnics of Spontaneously Hypertensive Rats in Conscious State

Depressor Responses of the Spontaneously Hypertensive Rats to the Anti-Hypertensive Agents

Rostral ventrolateral medulla as a site for the central hypertensive action of kinins.

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