Blood pressure of sinoaortic-denervated dogs is not increased by cardiac denervation

Although blood pressure rises markedly after acute sinoaortic denervation, animals with chronic sinoaortic denervation have normal or only slightly elevated mean arterial pressures. The present study was performed to determine whether reflexes from cardiac receptors exert antihypertensive effects and thereby lower blood pressure in animals with chronic sinoaortic denervation. We made multiple measurements of blood pressures in dogs with chronic sinoaortic denervation before and after their hearts were denervated surgically. Mean arterial pressure after cardiac denervation (100.3 +/- 4.2 mm Hg) was not significantly different from the mean pressures recorded before cardiac denervation in these sinoaortic-denervated dogs (104.8 +/- 3.1 mm Hg). Also, mean heart rate after cardiac denervation (107.4 +/- 5.5 beats/min) did not differ significantly from the mean heart rate recorded before cardiac denervation (107.2 +/- 5.9 beats/min). Cardiac denervation did, however, appear to reduce the lability of both blood pressure and heart rate in sinoaortic-denervated dogs. We conclude that cardiac receptors are not responsible for maintaining arterial pressure within essentially normal limits in animals with chronic sinoaortic denervation.     

Alpha-adrenergic vasoconstrictor tone limits right coronary blood flow in exercising dogs

In exercising dogs, increased myocardial O2 consumption (MVO2) of the left ventricle is met primarily by hyperemia, whereas increased O2 extraction makes a greater contribution to right ventricular (RV) O2 supply. We hypothesized that alpha-adrenergic vasoconstrictor tone limits right coronary (RC) blood flow during exercise, forcing increased O2 extraction. This tone might also contribute to lesser RC vascular conductance at rest. Accordingly, RV O2 balance was examined at rest and during graded treadmill exercise before and during alpha-adrenergic blockade with phentolamine (1 mg/kg, i.v., n=6). The transmural distribution of RC flow was measured with radiolabeled microspheres in 4 additional dogs. At rest, alpha-adrenergic receptor blockade did not significantly increase RC flow or conductance. During exercise, alpha-adrenergic blockade increased RC flow and conductance responses to increased RV MVO2 by 25% and 60%, respectively. The transmural distribution of RC flow was not altered by exercise or by alpha-adrenergic blockade. Before alpha-adrenergic blockade, hyperemia provided 39%-66% of the additional O2 consumed by the right ventricle during graded exercise; after alpha-adrenergic blockade, hyperemia contributed 74%-85%. After alpha-adrenergic blockade, the slope of the relationship between RC venous PO2 and RV MVO2 became less steep, reflecting less O2 extraction due to enhanced hyperemia. Additional experiments were conducted on 5 anesthetized, open-chest dogs with constant RC perfusion pressure and beta-adrenergic blockade. The RC flow response to intracoronary norepinephrine was shifted to the left compared with that measured in the left coronary circulation, consistent with observations in the conscious exercising dogs. In conclusion, alpha-adrenergic vasoconstrictor tone does not restrict resting RC blood flow, but during exercise, this tone transmurally blunts RC hyperemia and forces the right ventricle to mobilize its O2 extraction reserve. This effect is more pronounced than has been reported for the left ventricle.     

Analysis of bronchovascular downstream blood pressure changes in exercising sheep

The relative roles of neural and pressure gradient factors, causing a fall or maintenance of bronchial blood flow in exercising sheep, are unknown. These were examined in sheep prepared under thiopentone/isoflurane general anaesthesia with a pulsed Doppler probe mounted on the bronchial artery, and aortic pressure (Pa) catheter in superficial cervical artery. After recovery, Swan-Ganz catheters were inserted under local anaesthesia into the pulmonary artery. Bronchial flow and conductance (Qbr, Cbr), and pressure gradients (Pg; i.e. aortic minus right atrial, Pg_RAP; pulmonary artery, Pg_Ppa; and, left atrial (wedge) Pg_LAP) were derived from continuous records, after switching between downstream sites during and after moderately severe treadmill exercise (3.8 km.h(-1), for 1.7 min, 6 min recovery). The protocol was repeated after combined alpha1,alpha2-adrenoceptor/cholinoceptor blockade using phentolamine methanesulfonate and methscopolamine bromide. Bronchial flow fell in both receptor intact (INT) and (BL) blocked state. Pa rose in INT, but downstream pressures rose only 3.7 (RAP), 2.8 (Ppa) and 2.0 (LAP) mmHg (P for each < 0.05) in both INT and BL. Pg_RAP and Pg_Ppa did not rise, but Pg_LAP rose 4.0 mmHg (P < 0.05). In BL, Pa fell, as did Pg_RAP (7.0 mmHg, P < 0.05), Pg_Ppa (8.9 mmHg, P < 0.001), but Pg_LAP did not change. Thus, downstream pressures change by small amounts, and pressure gradients to RAP and Ppa sites do not change during moderately severe exercise in normal sheep. The fall in Qbr in INT is due to neural factors, but in BL is due to a fall in Pg. The relative rise in Pg_LAP in both INT and BL favours redistribution within total Qbr to the pulmonary capillary/vein/left atrium site.     

Relationship between turnover rate and blood concentration of lactate in exercising dogs.

Steady-state blood lactate concentrationss and lactate turnover, or entry, rates were determined by use of constant infusion of L(+)-[14C]lactate in seven anesthetized dogs before and during electrically induced exercise. Lactate entry rates increased during exercise in all dogs with or without the infusion of additional exogenous cold lactate. Blood lactate concentrations, on the other hand, rose to levels considerably below those predicted for these entry rates in a previous study of the relationship in normal nonexercising dogs. It is concluded that improved efficiency of lactate removal during exercise allows low blood concentrations despite large increases in entry rates.     

Renal reflexes in the regulation of blood pressure and sodium excretion

The rich innervation of the kidney is distributed to all structures of renal parenchyma thus providing important anatomical support to the functional evidence that the renal nerves can control kidney functions and send signals on the kidney environment to the central nervous system. Efferent renal nerve fibres are known to influence renal haemodynamics by modifying arteriolar vascular tone, renin release by a direct action on juxtaglomerular cells, and the excretion of sodium and water by changing tubular reabsorption of sodium and water at the different tubular levels. Mechano- and chemo-receptors have been shown in the kidney. Afferent fibres connected with renal receptors convey signals to the central nervous system both at spinal and supraspinal levels. The central areas receiving inputs from the kidney are those involved in the control of cardiovascular homeostasis and fluid balance. Activation of renal receptors by the electrical stimulation of renal afferent fibres were found to elicit both excitatory and inhibitory sympathetic responses. Although the existence of excitatory renorenal reflexes has been suggested, electrophysiological and functional data demonstrate that neural renorenal reflexes exert a tonic inhibitory influence on the tubular sodium and water reabsorption and on the secretion of renin from the juxtaglomerular cells.     

Effects of verapamil on sympathetic tone in normal and chronic sinoaortic-denervated conscious dogs

Previous studies have shown that calcium channel blockers from the dihydropyridine group (such as nicardipine) induce an increase in sympathetic tone from a central origin in chronic sinoaortic-denervated (SAD) dogs. In the present study, we investigated to see if verapamil possesses such properties. The effects of acute injection of verapamil (0.2 mg/kg i.v.) were compared in normal and SAD conscious dogs. Verapamil induced a decrease in blood pressure in the two groups of animals, and an increase in heart rate and plasma catecholamines (noradrenaline and adrenaline) in normal but not in SAD dogs. Contrary to the dihydropyridine studies (nicardipine), we did not find any evidence for a centrally mediated sympathoexcitatory effect of verapamil in conscious SAD dogs.     

Seasonal and diurnal melatonin production in exercising sled dogs

Melatonin is a hormone that is released from the pineal gland into the blood stream and is controlled by nerve impulses from the suprachiasmatic nuclei. Melatonin synthesis, which is inhibited by light on the mammalian retina, peaks in plasma concentrations during the night. Though still a subject of intense research, melatonin in mammals is known to effect the reproductive system, thyroid function, and adaptations to seasonal changes. Sled dogs in Fairbanks, Alaska (65 degrees N) can be exposed to anywhere from 21 h of daylight in the summer to 4 h in the winter. While light may be the primary factor influencing melatonin production, we hypothesized that exercise may also affect melatonin production. In the current study, sled dogs were used to study seasonal and diurnal variation in melatonin production. Sled dogs by nature are elite athletes and therefore exercise was a focus in the study. Both exercise and non exercise dogs from 2 distinct latitudes were used. The peak in melatonin production was prolonged in high latitude dogs (65 degrees N), compared with lower latitude dogs (45 degrees N). Dogs at both latitudes show a reduction in peak melatonin levels with exercise, and winter melatonin levels in both locations were higher than the summer. Surprisingly, sled dogs in Alaska had lower melatonin levels than sled dogs in New York.     

Auscultatory indirect measurement of blood pressure in dogs

An indirect method of measuring blood pressure (cuff plus stethoscope) was evaluated in 70 dogs weighing 15 to 30 kg (17.5 +/- 8.8 kg; mean +/- standard deviation). A cuff 12 cm wide was used. The measurements were most audible with the cuff on the upper foreleg of the dog and with the stethoscope placed in the medial epicondylar region just distal to the cuff. The cuff was inflated to greater than systolic pressure and allowed to deflate slowly. In 70 lightly sedated dogs, systolic blood pressures averaged 145 +/- 25 mmHg (mean +/- standard deviation) and diastolic blood pressures averaged 84 +/- 14 mmHg. Indirect measurements were compared to direct measurements (femoral arterial catheter). Systolic pressures obtained by this direct method averaged 138 +/- 29 mmHg (mean +/- standard deviation) and diastolic pressures averaged 84 +/- 17 mmHg. The correlation coefficient for systolic pressure was 0.96 and for diastolic pressure 0.97.     

Long-term estrogen deficiency lowers regional blood flow, resting systolic blood pressure, and heart rate in exercising premenopausal women

The cardiovascular consequences of hypoestrogenism in premenopausal women are unclear. Accordingly, the influence of menstrual status and endogenous estrogen (E(2)) exposure on blood pressure (BP), heart rate (HR), and calf blood flow in young (18-35 yr) regularly exercising premenopausal women with exercise-associated menstrual aberrations was investigated. Across consecutive menstrual cycles, daily urinary ovarian steroid levels were analyzed, and the area under the curve was calculated to determine menstrual status and E(2) exposure. BP, HR, blood flow, vascular conductance, and resistance were measured at baseline and following ischemic calf exercise. Exercising subjects consisted of 14 ovulatory (ExOv), 10 short-term (anovulatory and 100 days amenorrhea; LT-E(2) Def) E(2)-deficient women. Nine sedentary ovulatory subjects (SedOv) were also studied. All groups were similar in age (24.8 +/- 0.7 yr), height (164.8 +/- 1.3 cm), weight (57.9 +/- 0.9 kg), and body mass index (21.3 +/- 0.3 kg/m(2)). E(2)-deficient groups had lower (P < 0.002) E(2) exposure compared with ovulatory groups. Resting systolic BP, HR, blood flow, and vascular conductance were lower (P < 0.05) and vascular resistance higher (P < 0.05) in LT-E(2) Def compared with both ovulatory groups. Peak ischemic blood flow, vascular conductance, and HR were also lower (P < 0.05) and vascular resistance higher (P < 0.05) in LT-E(2) Def compared with all other groups. Our findings show that exercising women with long-term E(2) deficiency have impaired regional blood flow and lower systolic BP and HR compared with exercising and sedentary ovulatory women. These cardiovascular alterations represent markers of altered vascular function and autonomic regulation of which the long-term effects remain unknown.