Assessment of Autonomic and Non-Autonomic Components of Resting Hindlimb Vascular Resistance and Reactivity to Pressor Substances in Renal Hypertensive Rabbits

Angus, James A.; West, MJ; Korner, Paul I.

doi:10.1042/cs051057s

Cited by 7 publications

(5 citation statements)

References 6 publications

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“…Hamilton and Reid (1 983) reported that in conscious renal hypertensive rabbits there was a selective shift in ED50 during administration of a]-adrenoceptor agonists. This agonist-selective finding was in contrast to earlier studies from this laboratory (Angus et al 1976). The aim of the present study was to re-examine the constrictor and dilator responsiveness of the conscious rabbit hindquarter vasculature in the absence of cardiovascular reflexes by obtaining full dose-response curves under steady-state conditions.…”

Section: Introductioncontrasting

confidence: 57%

Hypertension Alters Slope and Range but Not Sensitivity to Vasoconstrictor and Vasodilator Agents in the Rabbit Hindquarter

Wright

Angus

Korner

1986

Clin Exp Pharma Physio

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The vascular reactivity (slope and range) and location parameter (ED50) of dose-response curves in the hindquarter vascular bed in conscious rabbits previously subjected to renal cellophane wrapping or sham operation were examined. The animals were instrumented with pulsed Doppler flow transducers and chronic indwelling aortic catheters for intra-arterial drug infusion. The rabbits were ganglion-blocked with mecamylamine before constructing full dose-response curves to intra-arterial infusions of methoxamine, noradrenaline, angiotensin II, acetylcholine, adenosine and serotonin. Curves relating dose to conductance were fitted to the experiments involving constrictors and curves relating dose to vascular resistance fitted to those involving dilator drugs. With both classes of drugs the reactivity was significantly higher in the hypertensive animals than in sham-operated rabbits. There was no difference in sensitivity (ED50 value) between the hypertensive and control animals for any agonist tested. The increased reactivity, but not sensitivity, could be entirely accounted for by the vascular amplifier action of medial hypertrophy in hypertension.

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Section: Introductioncontrasting

confidence: 57%

Hypertension Alters Slope and Range but Not Sensitivity to Vasoconstrictor and Vasodilator Agents in the Rabbit Hindquarter

Wright

Angus

Korner

1986

Clin Exp Pharma Physio

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“…A further factor involved as the systemic blood pressure gradually rises is an amplified vascular response perhaps due to hypertrophy of the media of the resistance vessels (Folkow, 1978). In rabbits with established cellophane-wrap hypertension, this amplification factor to a given dose of either noradrenaline, angiotensin I1 or vasopressin is about 2 in the hind limb (West, Angus & Korner, 1975;Angus, West& Korner, 1976) and about 1.5 in the whole body (West, 1974). This would contribute to further elevation of blood pressure and to further medial hypertrophy until a new steady state is eventually established.…”

Section: Development O F Renal Wrap Hypertensionmentioning

confidence: 99%

The Present Status of the Autoregulation Theory of the Pathogenesis of Hypertension

Korner

1980

Clin Exp Pharma Physio

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1. The autoregulation theory of hypertension has been attractive because it postulates a mechanism whereby an early rise in cardiac output becomes "transformed" through normal autoregulatory processes into an elevated total peripheral resistance. 2. "Normal" autoregulation involved in control of blood flow of regional beds is a rapid process compared with the slow changes postulated by the autoregulation theory. 3. Evidence is presented that under appropriate experimental conditions " volume" factors (cardiac output) and "constrictor" factors exert independent long-term effects in developing and in established hypertension. There is little evidence to support the autoregulation theory of hypertension.

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“…By contrast, Folkow et al 3 studied the local properties of isolated, perfused vascular beds, and this was also largely the case in our experiments in conscious animals in which autonomic reflexes were eliminated. 4 ' 5 Another difference was that we studied the effects of drugs on vascular resistance in our earlier studies, 4 ' 5 whereas Hamilton and Reid 7 measured only blood pressure responses, which depend not only on resistance changes but also on cardiac factors.…”

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confidence: 99%

Vascular amplifier properties in renovascular hypertension in conscious rabbits. Hindquarter responses to constrictor and dilator stimuli.

Wright¹,

Angus²,

Korner³

1987

Hypertension

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SUMMARY The local responses of the resistance vessels of the hindquarters of conscious, renal hypertensive (cellophane wrap) and sham-operated normotensive rabbits were studied during infusions of constrictor (norepinephrine, methoxamine, angiotensin II) and dilator (acetylcholine, adenosine, serotonin) drugs. The rabbits had implanted Doppler ultrasonic flow probes on the lower aorta and an indwelling catheter for intra-arterial infusion of drugs. Autonomic blockade with mecamylamine and propranolol was used to determine local vascular effects of each drug uncomplicated by reflex changes. Logistic dose-vascular response curves were characterized by (1) their range from resting to maximum response, (2) their 50% effective dose (i.e., sensitivity or dose at middle of the response range), and (3) the average slope about the 50% effective dose. At maximum dilatation the vascular resistance was about 70% greater in hypertensive rabbits than in normotensive rabbits. There were no significant differences in 50% effective dose values between curves for hypertensive and normotensive rabbits for constrictor or dilator drugs. However, with all drugs the hypertensive rabbits showed about twice the change in vascular resistance per unit dose compared with the normotensive rabbits. These results suggest that hypertrophy of the muscles of the precapillary vessels makes them a nonspecific amplifier of vascular resistance changes evoked by constrictor and dilator stimuli. They do not support previous claims of specific changes in "sensitivity" or claims that local amplifier action is unimportant in hypertension. (Hypertension 9: 122-131, 1987) KEY WORDS reactivity amplifier properties • constrictors • dilators * hypertension • vascular T HE amplifier properties of the hypertrophied vascular and cardiac musculature in primary and many types of secondary hypertension have been considered to play a role in the hemodynamic patterns of hypertension and most circulatory responses.1 ' 2 Folkow et al. 3 pointed out that the associated increase in the ratio of the wall thickness to lumen radius was important in making the small arteries and arterioles hemodynamic amplifiers of stimuli affecting vascular resistance. As a result, a given dose of constrictor agent or a given percentage shortening of the muscle would produce more pronounced vascular narrowing in hypertension than in normal vessels. This response has now been demonstrated in the isolated vessels of the limb and kidney in spontaneously hyper- Received October 1, 1985; accepted August 19, 1986. tensive rats (SHR), in rats with renal hypertension, and in the cutaneous circulation of patients with primary hypertension. 12 We have confirmed these amplifier properties in conscious rabbits with established renovascular (cellophane wrap) hypertension in which reflex influences on the circulation were abolished by autonomic blockade. 4 Moreover, we found similar enhancement of responsiveness to norepinephrine, angiotensin II, and vasopressin, which is in accord with nonspecific...

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Assessment of Autonomic and Non-Autonomic Components of Resting Hindlimb Vascular Resistance and Reactivity to Pressor Substances in Renal Hypertensive Rabbits

Cited by 7 publications

References 6 publications

Hypertension Alters Slope and Range but Not Sensitivity to Vasoconstrictor and Vasodilator Agents in the Rabbit Hindquarter

Hypertension Alters Slope and Range but Not Sensitivity to Vasoconstrictor and Vasodilator Agents in the Rabbit Hindquarter

The Present Status of the Autoregulation Theory of the Pathogenesis of Hypertension

Vascular amplifier properties in renovascular hypertension in conscious rabbits. Hindquarter responses to constrictor and dilator stimuli.

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