Body fluids and plasma atrial peptide after its chronic infusion in hypertensive rats

To determine the role of body fluid volume in the chronic hypotensive effect of atrial natriuretic factor (ANF), spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were infused with the peptide (Arg 101-Tyr 126) at a rate of 100 ng/h/rat for 5 days. Blood pressure (BP) was decreased from 176 +/- 4 to 133 +/- 3 mmHg in the SHR group 4 days after ANF infusion was initiated, whereas no changes were observed in ANF-infused WKY animals. Starting 5 days after the infusion began, body fluid measurements revealed no differences in plasma, blood and extracellular fluid volumes or in interstitial spaces. BP and plasma ANF concentrations were determined in another set of experiments before, during and after chronic ANF infusion. BP declined from 169 +/- 3 to 133 +/- 5 mmHg in SHR 5 days after the infusion commenced, but returned to basal values by day 10 or 11. Plasma ANF was significantly higher in SHR than in WKY rats throughout the observation period. However, there were no discernible changes in this parameter in ANF-infused SHR compared to non-infused SHR. A 3-fold rise in plasma ANF was noted in infused WKY rats at day 3 only. It is concluded that the chronic hypotensive effect of ANF in hypertensive animals is not related to changes in either body fluid volume or distribution. Moreover, the finding that chronic ANF infusion reduces BP in SHR without altering its plasma levels suggests a rapid ANF turnover.     

Dynamic characteristics of baroreflex neural and peripheral arcs are preserved in spontaneously hypertensive rats

Although baroreceptors are known to reset to operate in a higher pressure range in spontaneously hypertensive rats (SHR), the total profile of dynamic arterial pressure (AP) regulation remains to be clarified. We estimated open-loop transfer functions of the carotid sinus baroreflex in SHR and Wistar Kyoto (WKY) rats. Mean input pressures were set at 120 (WKY??? and SHR???) and 160 mmHg (SHR???). The neural arc transfer function from carotid sinus pressure to efferent splanchnic sympathetic nerve activity (SNA) revealed derivative characteristics in both WKY and SHR. The slope of dynamic gain (in decibels per decade) between 0.1 and 1 Hz was not different between WKY??? (10.1 ± 1.0) and SHR??? (10.4 ± 1.1) but was significantly greater in SHR??? (13.2 ± 0.8, P < 0.05 with Bonferroni correction) than in SHR???. The peripheral arc transfer function from SNA to AP showed low-pass characteristics. The slope of dynamic gain (in decibels per decade) did not differ between WKY??? (-34.0 ± 1.2) and SHR??? (-31.4 ± 1.0) or between SHR??? and SHR??? (-32.8 ± 1.3). The total baroreflex showed low-pass characteristics and the dynamic gain at 0.01 Hz did not differ between WKY??? (0.91 ± 0.08) and SHR??? (0.84 ± 0.13) or between SHR??? and SHR??? (0.83 ± 0.11). In both WKY and SHR, the declining slope of dynamic gain was significantly gentler for the total baroreflex than for the peripheral arc, suggesting improved dynamic AP response in the total baroreflex. In conclusion, the dynamic characteristics of AP regulation by the carotid sinus baroreflex were well preserved in SHR despite significantly higher mean AP.     

A possible explanation of genetic hypertension in the spontaneously hypertensive rat

Converting enzyme inhibitors prevent the development of hypertension and normalize arterial blood pressure in spontaneously hypertensive rats (SHR), suggesting a critical role for angiotensin II in genetic hypertension. We hypothesized that the SHR is hyperresponsive to the slow-pressor effect of angiotensin II. To test this hypothesis, 14 SHR and 14 normotensive Wistar Kyoto rats (WKY) were treated chronically with captopril (100 mg X kg-1 X day-1 in drinking water) beginning at 5 weeks of age. At 9 weeks of age, either angiotensin II (125 ng/min; 7 SHR and 7 WKY) or vehicle (7 SHR and 7 WKY) was infused for 2 weeks via an osmotic minipump implanted into the peritoneal cavity. Captopril treatment was maintained and systolic blood pressure was monitored 3 times weekly. Although systolic blood pressure was similar in SHR and WKY infused with vehicle (101 +/- 2 versus 103 +/- 5 mmHg, respectively during the second week), systolic blood pressure in SHR treated with angiotensin II was much greater than systolic blood pressure in WKY treated with angiotensin II (193 +/- 9 versus 132 +/- 11 mmHg, respectively during the second week, p less than 0.001). These results indicate that compared to WKY, SHR are remarkably more sensitive to the slow-pressor effect of chronic, low-dose infusions of angiotensin II. Our results support the hypothesis that the critical genetic defect in SHR is a change in the sensitivity to the slow-pressor effect of angiotensin II.     

Chronic infusion of low doses of atrial natriuretic factor (ANF Arg 101-Tyr 126) reduces blood pressure in conscious SHR without apparent changes in sodium excretion

Conscious SHR and WKY rats were infused during 7 days with synthetic ANF (Arg 101-Tyr 126), 100 ng/hr/rat (35 pmol/hr/rat) by means of miniosmotic pumps. The SHR initial blood pressure of 177 +/- 5 mmHg gradually dropped to 133 +/- 3 and 142 +/- 4 mmHg the last two days of infusion. No significant change in blood pressure was observed in the ANF-infused WKY group. No apparent difference in natriuresis or diuresis was observed in ANF-infused SHR and WKY when compared with non-infused control groups. A slight but significant lower immunoreactive ANF concentration was found in the atria of SHR than in their normotensive controls. No difference in cardiac weight was found between infused and non-infused rats. It is suggested that the hypotensive response observed in SHR and not in WKY is due to a decrease in vascular peripheral resistance. Whether ANF is involved in the development and maintenance of high blood pressure in SHR remains to be elucidated.     

The effect of prolonged infusion and withdrawal of angiotensin II in the spontaneously hypertensive rat

In spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY), prolonged intravenous administration of angiotensin II (AII, 0.2 microgram X kg-1 X min-1 for 3h) resulted in similar increases in arterial blood pressure. Heart rate decreased in WKY and increased in SHR. At the end of the infusion, blood pressure dropped substantially in SHR, but not in WKY: at 5 h after AII withdrawal, blood pressure in SHR had fallen from a control value of 172 +/- 3.3 to 146 +/- 3.9 mmHg (p less than 0.01), whereas pressure in WKY had fallen from 116 +/- 3.0 to 107 +/- 4.2 mmHg (statistically non significant). Thus, pressure at 5 h after AII withdrawal was still substantially higher (p less than 0.01) in the SHR than in the WKY. The results demonstrate that the fall in blood pressure following withdrawal of a prolonged infusion of AII in SHR is much less than that reported to occur following withdrawal of a prolonged infusion of vasopressin (AVP) in SHR.     

alpha(2)-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

We examined the effect of alpha(2)-adrenoreceptor blockade in the nucleus of the solitary tract (NTS) on baroreflex responses elicited by electrical stimulation of the left aortic depressor nerve (ADN) in urethane-anesthetized spontaneously hypertensive rats (SHR, n = 11) and normotensive Wistar-Kyoto rats (WKY, n = 11). ADN stimulation produced a frequency-dependent decrease in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). In SHR, unilateral microinjection of idazoxan into the NTS markedly reduced baroreflex control of MAP, RSNA, and HR and had a disproportionately greater influence on baroreflex control of MAP than of RSNA. In WKY, idazoxan microinjections did not significantly alter baroreflex function relative to control vehicle injections. These results suggest that baroreflex regulation of arterial pressure in SHR is highly dependent on NTS adrenergic mechanisms. The reflex regulation of sympathetic outflow to the kidney is less influenced by the altered alpha(2)-adrenoreceptor mechanisms in SHR.     

Central cardiovascular effects of baclofen in spontaneously hypertensive rats

This study was conducted to investigate the effects of centrally administered baclofen on blood pressure and heart rate in conscious spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Administration of baclofen (1.0 microgram/kg) into the lateral cerebral ventricle (icv) produced an increase in mean arterial pressure (MAP) in both SHR and WKY rats. The increase in MAP was significantly lower in SHR (13 +/- 3 mmHg) when compared with WKY (27 +/- 5 mmHg). The changes in heart rate (HR) were variable, from no change to a very small increase and did not differ significantly between SHR and WKY rats. The ability of baclofen to interfere with baroreceptor reflexes was also tested in separate experiments. In SHR, icv injection of baclofen (1.0 microgram/kg) significantly suppressed the pressor response and bradycardia evoked by phenylephrine 3.0 micrograms/kg iv, whereas in WKY, the pressor and HR responses to similar injections of phenylephrine were not affected by icv baclofen. Similarly, baclofen treatment modified hypotensive response and reflex tachycardia induced by nitroprusside (10.0 micrograms/kg) iv in SHR but not in WKY rats. Administration of sympathetic ganglionic blocker hexamethonium (HEX; 25 mg/kg) iv produced an equivalent decrease in MAP between SHR and WKY following icv injection of baclofen (1.0 microgram/kg). These results suggest that the effects of baclofen on the baroreceptor reflexes in SHR may not be mediated by a change in peripheral sympathetic tone.     

Sodium homeostasis in transplanted rats with a spontaneously hypertensive rat kidney

Recipients of a kidney from spontaneously hypertensive rats (SHR) but not from normotensive Wistar-Kyoto rats (WKY) develop posttransplantation hypertension. To investigate whether renal sodium retention precedes the development of posttransplantation hypertension in recipients of an SHR kidney on a standard sodium diet (0.6% NaCl), we transplanted SHR and WKY kidneys to SHR x WKY F1 hybrids, measured daily sodium balances during the first 12 days after removal of both native kidneys, and recorded mean arterial pressure (MAP) after 8 wk. Recipients of an SHR kidney (n = 12) retained more sodium than recipients of a WKY kidney (n = 12) (7.3 +/- 10 vs. 4.0 +/- 0.7 mmol, P < 0.05). MAP was 144 +/- 6 mmHg in recipients of an SHR kidney and 106 +/- 5 mmHg in recipients of a WKY kidney (P < 0.01). Modest sodium restriction (0.2% NaCl) in a further group of recipients of an SHR kidney (n = 10) did not prevent posttransplantation hypertension (MAP, 142 +/- 4 mmHg). Urinary endothelin and urodilatin excretion rates were similar in recipients of an SHR and a WKY kidney. Transient excess sodium retention after renal transplantation may contribute to posttransplantation hypertension in recipients of an SHR kidney.     

High flaxseed (linseed) diet restores endothelial function in the mesenteric arterial bed of spontaneously hypertensive rats.

The effect of high flaxseed diet (HFD) on blood pressure (BP) and mesenteric arterial bed (MAB) reactivity was studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. HFD did not affect BP in either SHR (control, 157 +/- 3; HFD, 153 +/- 3 mmHg) or WKY (control, 114 +/- 2; HFD, 117 +/- 2 mmHg) rats. Increases in perfusion pressure of the endothelium-intact MAB to phenylephrine and norepinephrine were higher (p < 0.05) in SHR than in WKY rats and the HFD failed to alter these responses. Vasorelaxant responses to acetylcholine (ACh) and bradykinin (BK) were greater (p < 0.05) in SHR maintained on HFD compared to SHR on control diet. While HFD also enhanced ACh responses in WKY, the effect was less than in SHR. Responses to sodium nitroprusside (SNP), were similar in all groups. Since ACh and BK-induced responses of the MAB were augmented in SHR on HFD, with no changes in BP, it is suggested that HFD improves endothelial vasorelaxant function through a pressure-independent mechanism.     

A new inbred Wistar-Kyoto rat substrain exhibiting apparent salt sensitivity and borderline hypertension

The normotensive Wistar-Kyoto (WKY) rat strain is a traditional control for the spontaneously hypertensive rat (SHR). We found trait differences between two inbred normotensive WKY strains, derived originally from different vendors, and compared these two strains from La Jolla-Taconic Farms (WKY/lj-tf) and La Jolla-Charles River (WKY/lj-cr) with the inbred SHR/lj-cr for cardiovascular, diurnal, and activity traits under normal and high (8%) NaCl diets. Marked genetic diversity was found between the two vendor-derived WKY. By using an extended study design and radiotelemetry, we compared WKY/lj-cr, WKY/lj-tf, and SHR/lj-cr with the following results: systolic pressure (120 +/- 1, 133 +/- 1, 168 +/- 3 mmHg, respectively); diurnal variation in heart rate (DeltaHR: 46 +/- 3, 71 +/- 4, 57 +/- 2 beats/min, respectively); and salt sensitivity of arterial pressure (Deltasystolic: 10 +/- 1, 21 +/- 1, 20 +/- 1 mmHg, respectively). The WKY/lj-tf genotype apparently results in compromised control of arterial pressure and heart rate, especially during high NaCl intake, and greater susceptibility to high pressure (i.e., high NaCl-induced secondary changes). WKY/lj-tf thus constitutes a new inbred borderline hypertensive WKY substrain offering unique opportunities for genomic studies into the development of genetic hypertension.     

Modulation of arterial baroreflex control of heart rate by skin cooling and heating in humans.

The purpose of this study was to examine the effects of skin cooling and heating on the heart rate (HR) control by the arterial baroreflex in humans. The subjects were 15 healthy men who underwent whole body thermal stress (esophageal temperatures, approximately 36.8 and approximately 37.0 degrees C; mean skin temperatures, approximately 26.4 and approximately 37.7 degrees C, in skin cooling and heating, respectively) produced by a cool or hot water-perfused suit during supine rest. The overall arterial baroreflex sensitivity in the HR control was calculated from spontaneous changes in beat-to-beat arterial pressure and HR during normothermic control and thermal stress periods. The carotid baroreflex sensitivity was evaluated from the maximum slope of the HR response to changes in carotid distending pressure, calculated as mean arterial pressure minus neck pressure. The overall arterial baroreflex sensitivity at existing arterial pressure increased during cooling (-1.32 +/- 0.25 vs. -2.13 +/- 0.20 beats. min(-1). mmHg(-1) in the control and cooling periods, respectively, P < 0.05), whereas it did not change significantly during heating (-1.39 +/- 0. 23 vs. -1.40 +/- 0.15 beats. min(-1). mmHg(-1) in the control and heating periods, respectively). Neither the cool nor heat loadings altered the carotid baroreflex sensitivity in the HR control. These results suggest that the sensitivity of HR control by the extracarotid (presumably aortic) baroreflex was augmented by whole body skin cooling, whereas the sensitivities of HR control by arterial baroreflex remain unchanged during mild whole body heating in humans.     

Antihypertensive effects of I-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine on plasma renin activity and catecholamine responses in spontaneously hypertensive rats

Fourteen 23 week old male spontaneously hypertensive rats (SHR) were randomly divided into saline control or phospholipid (I-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine) treatment groups. Four weeks of baseline systolic blood pressure (SBP) and heart rate (HR) measurements were determined via tail plethysmography. On week 25 of the baseline period a 1.5 ml blood sample was taken by tail clip for analysis of norepinephrine (NE), epinephrine (E), and plasma renin activity (PRA). On the following week, a single injection of phospholipid (11 ug/kg, s.c.) was given to the experimental animals following baseline SBP and HR determinations. A similar procedure was employed for control subjects, except they received an injection of normal saline (0.5 ml, s.c.). Systolic BP and HR responses were monitored for 24 minutes following the injection. A 1.5 ml blood sample was taken at the end of the 4th minute for NE, E, and PRA assays. A significant drop in SBP (202 +/- 5 mmHg to 124 +/- 6 mmHg) and an increase in HR (431 +/- 17 bpm to 519 +/- 21 bpm) were observed for experimental animals, but not for control subjects. Plasma NE increased significantly (446 +/- 42 pg/ml to 1099 +/- 77 pg/ml), but E remained unchanged following treatment with the phospholipid. Plasma renin activity increased for both groups, but this change was only significant for the experimental group (18.1 +/- 5.7 ng Al/ml/hr to 34.3 +/- 3.6 ng Al/ml/hr). Thus, it appears that I-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine is a potent antihypertensive vasodilating agent which stimulates baroreceptor mediated sympathetic discharge to the heart and kidneys of the SHR.     

Baroreflex modulation by angiotensins at the rat rostral and caudal ventrolateral medulla

We determined the effect of microinjection of ANG-(1-7) and ANG II into two key regions of the medulla that control the circulation [rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively)] on baroreflex control of heart rate (HR) in anesthetized rats. Reflex bradycardia and tachycardia were induced by increases and decreases in mean arterial pressure produced by intravenous phenylephrine and sodium nitroprusside, respectively. The pressor effects of ANG-(1-7) and ANG II (25 pmol) after RVLM microinjection (11 +/- 0.8 and 10 +/- 2 mmHg, respectively) were not accompanied by consistent changes in HR. In addition, RVLM microinjection of these angiotensin peptides did not alter the bradycardic or tachycardic component of the baroreflex. CVLM microinjections of ANG-(1-7) and ANG II produced hypotension (-11 +/- 1.5 and -11 +/- 1.9 mmHg, respectively) that was similarly not accompanied by significant changes in HR. However, CVLM microinjections of angiotensins induced differential changes in the baroreflex control of HR. ANG-(1-7) attenuated the baroreflex bradycardia (0.26 +/- 0.06 ms/mmHg vs. 0.42 +/- 0.08 ms/mmHg before treatment) and facilitated the baroreflex tachycardia (0.86 +/- 0.19 ms/mmHg vs. 0.42 +/- 0.10 ms/mmHg before treatment); ANG II produced the opposite effect, attenuating baroreflex tachycardia (0.09 +/- 0.06 ms/mmHg vs. 0.31 +/- 0.07 ms/mmHg before treatment) and facilitating the baroreflex bradycardia (0.67 +/- 0.16 ms/mmHg vs. 0.41 +/- 0.05 ms/mmHg before treatment). The modulatory effect of ANG II and ANG-(1-7) on baroreflex sensitivity was completely abolished by peripheral administration of methylatropine. These results suggest that ANG II and ANG-(1-7) at the CVLM produce a differential modulation of the baroreflex control of HR, probably through distinct effects on the parasympathetic drive to the heart.     

Increased blood pressure in the offspring of diabetic mothers

Studies were conducted in rats to determine the effect of maternal diabetes and the consequent hyperglycemia on cardiovascular function in the offspring. Diabetes was induced in pregnant Wistar rats through streptozotocin injection (50 mg/kg). Cardiovascular parameters were measured in 2-mo-old offspring animals of diabetic (OD, n=12) and control rats (OC, n=8). Arterial pressure (AP), heart rate (HR), baroreflex sensitivity, and vascular responsiveness to phenylephrine (PH) and sodium nitroprusside (SN) were measured. Angiotensin-converting enzyme (ACE) activity in heart, kidney, and lung was determined. OD rats exhibited increases in systolic AP (138+/-8 vs. 119+/-6 mmHg, OD vs. OC), with no change in HR (342+/-21 vs. 364+/-39 beats per minute (bpm), OD vs. OC). The reflex tachycardia elicited by SN was reduced in OD rats, as indicated by the slope of the linear regression (-2.2+/-0.4 vs. -3.6+/-0.8 bpm/mmHg, OD vs. OC). Vascular responsiveness to PH was increased 63% in OD rats compared with OC. OD rats showed increases in ACE activity in heart, kidney, and lung (1.13+/-0.24, 3.04+/-0.86, 40.8+/-8.9 vs. 0.73+/-0.19, 1.7+/-0.45, 28.1+/-6 nmol His-Leu.min-1 mg protein-1, OD vs. OC). Results suggest that diabetes during pregnancy affects cardiovascular function in offspring, seen as hypertension, baroreflex dysfunction, and activation of tissue renin-angiotensin system.     

Decrease in urinary excretion of active kallikrein in conscious young and adult spontaneously hypertensive rats

Urinary excretion of active kallikrein was determined every day (amidolytic assay) in 6 male Okamoto-Aoki spontaneously hypertensive rats (SHR) and 6 male normotensive Wistar-Kyoto rats (WKY) from ages 4 to 7 weeks and from 12 to 15 weeks. The rats were housed in individual metabolic cages and were allowed free access to food having normal sodium content and to tap water. Urinary kallikrein excretion was lower in 4-week-old SHR than in age-matched WKY (7.8 +/- 1.4 vs. 15.5 +/- 2.3 nkat/24 h respectively, P less than 0.01) at a moment when systolic blood pressure (BP) in SHR was already higher than in WKY. The slope of the increase in active kallikrein excretion from week 4 to 7 was not different for SHR and WKY (6.34 +/- 1.05 vs. 7.50 +/- 1.02 nkat/24 h-1 . wk-1 respectively). In contrast, from week 12 to 15, this slope was not significant for SHR (1.67 +/- 2.55 nkat/24 h-1 . wk-1) while it remained positive in WKY (7.36 +/- 3,44 nkat/24 h-1 . wk-1). In both SHR and WKY, urinary kallikrein excretion was directly related to BP from week 4 to 7 but the slope of the regression line was less for SHR than for WKY (0.19 +/- 0.05 vs. 0.48 +/- 0.12 nkat/24 h-1 . mm Hg respectively). From ages 12 to 15 weeks, kallikrein excretion was still related to pressure in WKY (y = 1.92 x - 180.8; r = 0.93) but not in SHR (y = 0.71 x - 81.48; r = 0.52).(ABSTRACT TRUNCATED AT 250 WORDS)     

Indapamide-induced prevention of myocardial fibrosis in spontaneous hypertension rats is not nitric oxide-related

We studied the effect of thiazide-like diuretic--indapamide on fibrosis development in the left ventricle of young spontaneously hypertensive rats (SHR) and assessed the involvement of nitric oxide in this process. Six-week-old male SHR were treated with indapamide (1 mg/kg/day) for six weeks. Age-matched SHR were used as hypertensive and Wistar-Kyoto rats (WKY) as normotensive control. Systolic blood pressure was measured by tail-cuff plethysmography. Nitric oxide synthase (NOS) activity, protein expressions of endothelial (eNOS) and inducible NOS (iNOS), myocardial fibrosis and collagen type I and III were determined in the left ventricle. Indapamide treatment partially prevented SBP increase in SHR (SHR+Indapamide: 157+/-4, SHR: 171+/-3, WKY: 119+/-3 mmHg). Indapamide prevented myocardial fibrosis development in SHR, but without affecting collagen type I to type III ratio. Indapamide did not affect NOS activity as well as eNOS and iNOS protein expressions in the left ventricles evaluated by both Western blot and immunohistochemically. In conclusion, our results indicate that indapamide-induced prevention of myocardial fibrosis is not mediated by nitric oxide-related mechanism.     

The blood pressure decrease-induced sympathetic discharge following atrial natriuretic factor administration may offset its natriuretic action

Conscious SHR and WKY rats were infused during 7 days with ANF (Arg 101-Tyr 126), 100 ng/hr/rat, by means of miniosmotic pumps and their basal blood pressure (BP), changes in sodium excretion and urinary catecholamines compared with those at the last day of the infusion. The SHR initial BP of 181 +/- 3 mmHg gradually declined to 137 +/- 5 mmHg. No significant change in blood pressure was observed in the ANF-infused WKY group. However, WKY rats exhibited an increased sodium excretion and urinary dopamine/norepinephrine ratio when compared to sham-infused rats. No such differences were observed in SHR. It is suggested that an ANF-induced withdrawal of the renal sympathetic tone permits the manifestation of its natriuretic action in WKY rats. When, however, a BP decrease predominates, as in SHR, this decrease results in a reflex sympathetic discharge with a renal sympathetic activity over-riding the ANF induced natriuresis seen in WKY rats. Secondary sympathetic responses to the ANF-induced BP decrease have to be thus taken into account when a dissociation between the hypotensive and natriuretic action of ANF is observed in vivo.     

Cardiac sympathetic afferent stimulation impairs baroreflex control of renal sympathetic nerve activity in rats

It is well known that cardiac sympathetic afferent reflexes contribute to increases in sympathetic outflow and that sympathetic activity can antagonize arterial baroreflex function. In this study, we tested the hypothesis that in normal rats, chemical and electrical stimulation of cardiac sympathetic afferents results in a decrease in the arterial baroreflex function by increasing sympathetic nerve activity. Under alpha-chloralose (40 mg/kg) and urethane (800 mg/kg i.p.) anesthesia, renal sympathetic nerve activity, mean arterial pressure, and heart rate were recorded. The arterial baroreceptor reflex was evaluated by infusion of nitroglycerin (25 microg i.v.) and phenylephrine (10 microg i.v.). Left ventricular epicardial application of capsaicin (0.4 microg in 2 microl) blunted arterial baroreflex function by 46% (maximum slope 3.5 +/- 0.3 to 1.9 +/- 0.2%/mmHg, P < 0.01). When the central end of the left cardiac sympathetic nerve was electrically stimulated (7 V, 1 ms, 20 Hz), the sensitivity of the arterial baroreflex was similarly decreased by 42% (maximum slope 3.2 +/- 0.3 to 1.9 +/- 0.4%/mmHg; P < 0.05). Pretreatment with intracerebroventricular injection of losartan (500 nmol in 1 microl of artificial cerebrospinal fluid) completely prevented the impairment of arterial baroreflex function induced by electrical stimulation of the central end of the left cardiac sympathetic nerve (maximum slope 3.6 +/- 0.4 to 3.1 +/- 0.5%/mmHg). These results suggest that the both chemical and electrical stimulation of the cardiac sympathetic afferents reduces arterial baroreflex sensitivity and the impairment of arterial baroreflex function induced by cardiac sympathetic afferent stimulation is mediated by central angiotensin type 1 receptors.     

Baroreflex responses to electrical stimulation of aortic depressor nerve in conscious SHR

Baroreflex responses to changes in arterial pressure are impaired in spontaneously hypertensive rats (SHR). Mean arterial pressure (MAP), heart rate (HR), and regional vascular resistances were measured before and during electrical stimulation (5-90 Hz) of the left aortic depressor nerve (ADN) in conscious SHR and normotensive control rats (NCR). The protocol was repeated after beta-adrenergic-receptor blockade with atenolol. SHR exhibited higher basal MAP (150 +/- 5 vs. 103 +/- 2 mmHg) and HR (393 +/- 9 vs. 360 +/- 5 beats/min). The frequency-dependent hypotensive response to ADN stimulation was preserved or enhanced in SHR. The greater absolute fall in MAP at higher frequencies (-68 +/- 5 vs. -38 +/- 3 mmHg at 90-Hz stimulation) in SHR was associated with a preferential decrease in hindquarter (-43 +/- 5%) vs. mesenteric (-27 +/- 3%) resistance. In contrast, ADN stimulation decreased hindquarter and mesenteric resistances equivalently in NCR (-33 +/- 7% and -30 +/- 7%). Reflex bradycardia was also preserved in SHR, although its mechanism differed. Atenolol attenuated the bradycardia in SHR (-88 +/- 14 vs. -129 +/- 18 beats/min at 90-Hz stimulation) but did not alter the bradycardia in NCR (-116 +/- 16 vs. -133 +/- 13 beats/min). The residual bradycardia under atenolol (parasympathetic component) was reduced in SHR. MAP and HR responses to ADN stimulation were also preserved or enhanced in SHR vs. NCR after deafferentation of carotid sinuses and contralateral right ADN. The results demonstrate distinct differences in central baroreflex control in conscious SHR vs. NCR. Inhibition of cardiac sympathetic tone maintains reflex bradycardia during ADN stimulation in SHR despite impaired parasympathetic activation, and depressor responses to ADN stimulation are equivalent or even greater in SHR due to augmented hindquarter vasodilation.     

Cardiovascular Responses Induced by Obstructive Apnea Are Enhanced in Hypertensive Rats Due to Enhanced Chemoreceptor Responsivity

Spontaneously hypertensive rats (SHR), like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. The effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY). Blood pressure increased by 57±3 mmHg during apnea in SHR and by 28±3 mmHg in WKY (p<0.05, n = 14/13). The respiratory effort increased by 53±6 mmHg in SHR and by 34±5 mmHg in WKY. The heart rate fell by 209±19 bpm in SHR and by 155±16 bpm in WKY. The carotid chemoreceptors were then inactivated by the ligation of the carotid body artery, and apneas were induced two days later. The inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. The apnea-induced hypertension was 11±4 mmHg in SHR and 8±4 mmHg in WKY. The respiratory effort was 15±2 mmHg in SHR and 15±2 mmHg in WKY. The heart rate fell 63±18 bpm in SHR and 52±14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. In conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea.