Jang Y. Lee

Hemodynamic alterations in the young spontaneously hypertensive rat: elevated total systemic and hindquarter vascular resistance.

Summary Abdominal aortic blood flow and hindquarter vascular resistance were determined in young (2-3 mo) spontaneously hypertensive rats (SHR) and in age-matched Wistar Kyoto (WKY) normo-tensives. Abdominal aortic blood flow was similar in the 2 groups, whereas hindquarter vascular resistance was elevated in the SHR compared to WKY. Additionally, in the open-chest preparation there was no significant difference in ascending aortic blood flow between hypertensives and normoten-sives, while total peripheral resistance was increased in the SHR relative to WKY. These data suggest that early in the development of hypertension in the SHR the hemodynamic pattern of normal blood flow and elevated resistance exists in the hindquarter vasculature and the total systemic circulation.

Unaltered Distribution of Cardiac Output in the Conscious Young Spontaneously Hypertensive Rat: Evidence for Uniform Elevation of Regional Vascular Resistances

Radioactive microspheres (50 µ mdiameter) were injected into the left ventricle of conscious rats fasted for 12 h, and the percent distribution of cardiac output to major organs was

Systemic and regional haemodynamic effects of renal denervation in spontaneously hypertensive rats.

Systemic and regional haemodynamic effects of renal denervation were evaluated in adult (six-month-old) male spontaneously hypertensive rats (SHR) using the Fick procedure and electromagnetic flowmetry technique. Renal denervation (bilateral, 10% phenol in ethanol), performed five to eight days before the experiment, resulted in a significant decrease (-12%) in arterial pressure in conscious SHR (denervated = 182 +/- 4 versus sham = 207 +/- 8 mmHg, P less than 0.05) that was associated with a reduction in total peripheral resistance (TPR: denervated = 1.83 +/- 0.19 versus sham = 2.78 +/- 0.29 mmHg/ml/min, P less than 0.05) and an increase in cardiac output (denervated = 106 +/- 10 versus sham = 80 +/- 9 ml/min, P less than 0.05). Heart rate was not different between the two groups. Renal, hindquarter and superior mesenteric blood flows, determined under pentobarbital anaesthesia, of denervated SHR were not significantly different from sham values. Renal vascular resistance (mmHg/ml/min) was substantially reduced (-39%) in the denervated SHR (denervated = 25.1 +/- 1.86 versus sham = 41.1 +/- 3.48, P less than 0.01), but vascular resistances in the hindquarter and superior mesenteric beds were not reduced significantly. In this preparation TPR was reduced 32% in denervated SHR. The data demonstrate that renal denervation in adult SHR proves an antihypertensive vasodilator-like effect related to a decrease in TPR with increased cardiac output. The reduction in renal vascular resistance in denervated SHR may produce a major contribution to decreased TPR. Other beds may also contribute to the decrease in TPR, although to a lesser extent, since the decrease in TPR cannot be fully accounted for by decreased renal vascular resistance.

Intact hindquarter vascular responses of young spontaneously hypertensive rats to norepinephrine and tyramine

Abstract Intact hindquarter vascular responses to abdominal aortic injections of subpressor doses of norepinephrine (0.01, 0.02, 0.03 μg) or tyramine (5, 10, 15 μg) were examined in young ( 2 1 2 –3 months ) spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) normotensives to ascertain whether altered vascular response to catecholamines in SHR could be detected in the presence of relatively constant systemic arterial perfusion pressure. Increases in vascular resistance (Δ mmHg. min/ml) and total decreases in blood flow volume (Δ ml) were determined by using electromagnetic flowmetry and blood flow integration techniques. Under a resting condition the abdominal aortic flow rate (ml/min) was similar between the SHR (8.7 ± 0.5) and WKY control (9.1 ± 0.5), whereas hindquarter vascular resistance was greater (73.8%) in SHR than in WKY normotensives (P

Altered regional vasodilator responses to glossopharyngeal nerve stimulation in spontaneously hypertensive rats.

The hindlimb and renal vasodilator responses produced by electrical stimulation of the glossopharyngeal nerve were examined in adult (six to eight months) male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive rats to ascertain whether central neurogenically activated vasodilator capacity of these regional vascular beds is altered in SHR. Changes in systemic blood pressure and regional blood flow were simultaneously measured, and vascular resistance was calculated. Glossopharyngeal nerve stimulation (3.0 volts, 0.3 ms) at the frequency of 10 Hz resulted in a significantly greater vasodilation (% decrease in resistance) in SHR than in WKY control for both the hindlimb (SHR - 13.0 +/- 1.5% versus WKY - 3.4 +/- 1.6%, P less than 0.01) and renal (SHR - 7.6 +/- 0.6% versus WKY - 1.3 +/- 0.4%, P less than 0.01) vascular beds. The linear portion of the frequency-response curves of hindlimb or renal vasodilation of SHR was shifted parallel to the left of the WKY curve. Stimulus frequencies required to produce a 20% reduction in hindlimb resistance and a 10% reduction in renal resistance were lower in SHR (hindlimb 17.0 +/- 1.8 Hz; renal 19.9 +/- 1.4 Hz) than in WKY control (hindlimb 24.6 +/- 1.1 Hz; renal 39.3 +/- 4.8 Hz; P less than 0.01). The maximal vasodilator response to glossopharyngeal nerve stimulation in the hindlimb vascular bed was similar in SHR and WKY control, but in the renal vascular bed SHR showed a greater maximal response compared to WKY normotensives (SHR - 16.3 +/- 0.9% versus WKY - 12.7 +/- 1.6%, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of verapamil and nifedipine on systemic hemodynamics in spontaneously hypertensive rats.

Verapamil (1 mg/kg, i.v.) and nifedipine (0.3 mg/kg, i.v.) were tested at equi-antihypertensive doses for systemic hemodynamic responses in conscious spontaneously hypertensive rats (SHR) using the Fick method. Systemic hemodynamic effects of these agents were also evaluated in areflexic, spinal cord-transected and vagotomized SHR using the electromagnetic flowmetry technique. Both verapamil and nifedipine lowered mean arterial pressure (MAP:verapamil = -24%; nifedipine = -28%) in conscious SHR by decreasing total peripheral resistance (TPR:verapamil = -48%; nifedipine = -59%) with a concomitant rise in cardiac output (CO: verapamil = 48%; nifedipine = 86%) and stroke volume (SV:verapamil = 54%; nifedipine = 65%), but verapamil prevented tachycardia, whereas nifedipine increased heart rate (HR:13%). Verapamil and nifedipine also altered systemic hemodynamics in the areflexic SHR; verapamil reduced MAP (-31%) by reducing CO (-18%) with associated bradycardia (-25% HR), whereas nifedipine also lowered MAP (-21%) by decreasing TPR (-18%) without changes in CO and HR. It is concluded that, firstly, the antihypertensive action of verapamil and nifedipine in conscious SHR is due to systemic vasodilation that is associated with reflexly increased CO; secondly, that verapamil has a direct negative chronotropic effect, but nifedipine appears to be devoid of such an effect, and finally that the ability of verapamil to decrease TPR may depend upon resting sympathetic tone.

Reflex cardiovascular responses induced by electrical stimulation of glossopharyngeal nerves in the rat

Reflex cardiovascular responses to electrical stimulation of glossopharyngeal nerves (GPN) were studied in Dial-Urethane anesthetized rats. GPN stimulation at 3 V, 0.3 msec and 50 Hz produced maximal reflex depressor (34 +/- 2 mmHg) and bradycardia (21 +/- 2 beats/min) responses that were altered as follows: pentolinium (0.25 mg/kg, i.a.) blocked approximately 72% and 89% of control values of depressor and bradycardia responses, respectively; tripelennamine (5 mg/kg, i.a.) significantly reduced depressor responses (76%); whereas atropine (0.4 mg/kg i.a.) blocked only bradycardia (85%). Regional blood flow studies showed that GPN stimulation reduced systemic arterial pressure (approximately 25%), and increased iliac artery blood flow (5%), and decreased blood flow through the renal (14%) and superior mesenteric (13%) arteries. Hence, decreases in vascular resistance during GPN stimulation were greater in the hindlimb vascular bed (28%) than in the renal (14%) or the mesenteric vasculatures. In addition, the magnitude of decreases in hindlimb vascular resistance by GPN stimulation was reduced (80%) by pretreatment with tripelennamine, but not by atropine. The results suggest that reductions in arterial blood pressure and hindlimb vascular resistance of the rat in response to GPN stimulation may be mediated via a histaminergic vasodilator mechanism, and that there may be a differential pattern of reflex vascular adjustments of blood flow and vascular resistance among regional vasculatures of the rate.

Unaltered Maximum Reflex Vasodilatory Capacity of the Perfused Hindquarters of Spontaneously Hypertensive Rats

Hindquarter reflex vasodilation (RVD delta mmHg decrease in perfusion pressure) in response to arterial pressure elevations by intravenous norepinephrine (NE) was examined in young (2 1/2-3 months) and mature (8-10 months) spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) normotensive rats to ascertain whether maximum reflex vasodilatory capacity is altered in the developmental and/or established stages of spontaneous hypertension. The maximal RVD was not significantly different in young or mature SHR (young 26.2 +/- 1.9 and mature 36.2 +/- 3.2) compared to age-matched WKY controls (young 23.9 +/- 1.8 and mature 29.6 +/- 2.3) (P greater than 0.05 between SHR vs. WKY at both ages). However, the rise in mean systemic arterial pressure by NE which produced maximal RVD was greater in mature SHR (116.0 +/- 7.4 mmHg) than in WKY controls (78.3 +/- 6.2 mmHg) (P less than 0.01), whereas no such differences were found between young SHR (85.1 +/- 6.5 mmHg) and its WKY controls (87.5 +/- 2.3 mmHg). There was no difference in the dose of NE that required maximal responses of reflex vasodilation in young or mature SHR compared to WKY controls. In each age group of SHR or WKY rats, RVD was linearly related to the arterial pressure increments. The slope (a +/- SEM) of the regression line for the correlation between the pressure rises and resultant RVD was similar in young SHR (a = 0.424 +/- 0.061) and WKY controls of (a = 0.458 +/- 0.013). In contrast, the slope of the regression line for these two parameters in mature SHR (a = 0.250 +/- 0.004) was significantly smaller than that of either WKY controls (a = 0.364 +/- 0.010) or young SHR (P less than 0.01). The direct hindquarter vasodilation of mature SHR in response to intra-arterial administration of histamine or nitroglycerin was not different compared to that of WKY controls. The results indicate an unaltered maximum hindquarter reflex vasodilatory capacity during the developmental and established stages of genetic hypertension in SHR. An additional finding in the present study was the abnormal responsiveness of the baroreceptor reflex vasodilator system of mature SHR to a wide range of arterial pressure elevations. This abnormal responsiveness may contribute to the maintenance of high blood pressure in the established stage of hypertension.